SG175264A1 - Proline derivatives as cathepsin inhibitors - Google Patents
Proline derivatives as cathepsin inhibitors Download PDFInfo
- Publication number
- SG175264A1 SG175264A1 SG2011076114A SG2011076114A SG175264A1 SG 175264 A1 SG175264 A1 SG 175264A1 SG 2011076114 A SG2011076114 A SG 2011076114A SG 2011076114 A SG2011076114 A SG 2011076114A SG 175264 A1 SG175264 A1 SG 175264A1
- Authority
- SG
- Singapore
- Prior art keywords
- pyrrolidine
- carboxylic acid
- benzenesulfonyl
- cyano
- amide
- Prior art date
Links
- 108010084457 Cathepsins Proteins 0.000 title description 8
- 102000005600 Cathepsins Human genes 0.000 title description 8
- 239000003112 inhibitor Substances 0.000 title description 7
- 150000003147 proline derivatives Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 493
- 239000003814 drug Substances 0.000 claims abstract description 5
- UIVATUPCWVUVIM-UHFFFAOYSA-N 1-aminocyclopropane-1-carbonitrile Chemical compound N#CC1(N)CC1 UIVATUPCWVUVIM-UHFFFAOYSA-N 0.000 claims description 543
- -1 benzo[1,3]dioxolyl Chemical group 0.000 claims description 341
- 238000000034 method Methods 0.000 claims description 183
- 238000006243 chemical reaction Methods 0.000 claims description 98
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 47
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 44
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 claims description 42
- 125000001188 haloalkyl group Chemical group 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 125000005059 halophenyl group Chemical group 0.000 claims description 25
- 235000019253 formic acid Nutrition 0.000 claims description 23
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 19
- VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 17
- 125000003386 piperidinyl group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
- 201000001320 Atherosclerosis Diseases 0.000 claims description 11
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000003566 oxetanyl group Chemical group 0.000 claims description 10
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 7
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 7
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 7
- 208000002223 abdominal aortic aneurysm Diseases 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 208000007474 aortic aneurysm Diseases 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 7
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000006456 halo alkyl cycloalkyl group Chemical group 0.000 claims description 7
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- DJSZOSCFBLXRTG-UHFFFAOYSA-N 1-(benzenesulfonyl)-n-(cyanomethyl)-6,6-difluoro-2,3,5,7-tetrahydro-1h-pyrrolizine-8-carboxamide Chemical compound N#CCNC(=O)C12CC(F)(F)CN1CCC2S(=O)(=O)C1=CC=CC=C1 DJSZOSCFBLXRTG-UHFFFAOYSA-N 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- KXYZKSPGWZDZAC-CZUORRHYSA-N (2r,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CN=C1N1[C@@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 KXYZKSPGWZDZAC-CZUORRHYSA-N 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- CERMFEOPSKBJTC-MWSTZMHHSA-N (2R)-4-(2-chlorophenyl)sulfonyl-N-(1-cyanocyclopropyl)-1-[(2S)-1-methylpyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)[C@@H]1N(CC(C1)S(=O)(=O)C1=C(C=CC=C1)Cl)C(=O)[C@H]1N(CCC1)C CERMFEOPSKBJTC-MWSTZMHHSA-N 0.000 claims description 4
- NUWKRRSZDVBNBH-SQGPQFPESA-N (2r,4s,5r)-n-(1-cyanocyclopropyl)-5-(4-fluorophenyl)-2-(2-methylpropyl)-4-methylsulfonylpyrrolidine-2-carboxamide Chemical compound C1([C@@H]2[C@H](C[C@](N2)(CC(C)C)C(=O)NC2(CC2)C#N)S(C)(=O)=O)=CC=C(F)C=C1 NUWKRRSZDVBNBH-SQGPQFPESA-N 0.000 claims description 4
- ZDOMPVOUVBPMAB-PWSUYJOCSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 ZDOMPVOUVBPMAB-PWSUYJOCSA-N 0.000 claims description 4
- QLNVUPAGLNJEBS-MOPGFXCFSA-N (2s,4r)-4-(benzenesulfonyl)-n-(cyanomethyl)-1-(cyclohexylmethyl)pyrrolidine-2-carboxamide Chemical compound C([C@@H](C[C@H]1C(NCC#N)=O)S(=O)(=O)C=2C=CC=CC=2)N1CC1CCCCC1 QLNVUPAGLNJEBS-MOPGFXCFSA-N 0.000 claims description 4
- FOAMYQNXUWBTGW-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(pyridin-4-ylmethyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(CC=2C=CN=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 FOAMYQNXUWBTGW-AEFFLSMTSA-N 0.000 claims description 4
- LAQYCULJKIBPRG-UHFFFAOYSA-N 1-(2-tert-butylphenyl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)(C)C1=CC=CC=C1N1C(C(=O)NC2(CC2)C#N)CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 LAQYCULJKIBPRG-UHFFFAOYSA-N 0.000 claims description 4
- ODBDKMARACCPKY-UHFFFAOYSA-N 2-(benzenesulfonyl)-n-(cyanomethyl)-6,6-difluoro-2,3,5,7-tetrahydro-1h-pyrrolizine-8-carboxamide Chemical compound C1C2(C(=O)NCC#N)CC(F)(F)CN2CC1S(=O)(=O)C1=CC=CC=C1 ODBDKMARACCPKY-UHFFFAOYSA-N 0.000 claims description 4
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- HDIBSQXJZNHSTQ-YPMHNXCESA-N methyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 HDIBSQXJZNHSTQ-YPMHNXCESA-N 0.000 claims description 4
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 4
- JSYGPHPKKKWVDK-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-1-(2-phenylphenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)C1CN(C=2C(=CC=CC=2)C=2C=CC=CC=2)C(C(=O)NC2(CC2)C#N)C1 JSYGPHPKKKWVDK-UHFFFAOYSA-N 0.000 claims description 4
- GITCPOVUJAFOHR-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-1-(3-cyanophenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)C1CN(C=2C=C(C=CC=2)C#N)C(C(=O)NC2(CC2)C#N)C1 GITCPOVUJAFOHR-UHFFFAOYSA-N 0.000 claims description 4
- FKMVHIFCKGOXPM-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-1-[3-(trifluoromethyl)phenyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC(N2C(CC(C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=C1 FKMVHIFCKGOXPM-UHFFFAOYSA-N 0.000 claims description 4
- OKEQPYMHGAZLKW-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-1-naphthalen-1-yl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)C1CN(C=2C3=CC=CC=C3C=CC=2)C(C(=O)NC2(CC2)C#N)C1 OKEQPYMHGAZLKW-UHFFFAOYSA-N 0.000 claims description 4
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
- 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 claims description 4
- XCGZLWDQAQDHTK-IFMALSPDSA-N (2r,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1C[C@H](CN1C1=CC(=NN1CC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 XCGZLWDQAQDHTK-IFMALSPDSA-N 0.000 claims description 3
- VLXRPCUOCQQURI-SJLPKXTDSA-N (2r,4r)-4-(2-chloro-4-morpholin-4-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CCOCC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 VLXRPCUOCQQURI-SJLPKXTDSA-N 0.000 claims description 3
- OLUABKSCNUOOAJ-NVXWUHKLSA-N (2r,4r)-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 OLUABKSCNUOOAJ-NVXWUHKLSA-N 0.000 claims description 3
- CZCVHOZGJZYVFQ-DENIHFKCSA-N (2r,4r)-4-[2-chloro-4-(4-ethylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound C1CN(CC)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@H](C2)C(=O)NC2(CC2)C#N)C=2C(=CC=CN=2)C(F)(F)F)C(Cl)=C1 CZCVHOZGJZYVFQ-DENIHFKCSA-N 0.000 claims description 3
- SPZFBBAYXNSUJY-TZIWHRDSSA-N (2r,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclohexyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1C[C@H](CN1C1=CC(=NN1C1CCCCC1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 SPZFBBAYXNSUJY-TZIWHRDSSA-N 0.000 claims description 3
- HSEMOQSMMUHGHR-IFMALSPDSA-N (2r,4r)-n-(1-cyanocyclopropyl)-1-[2-(3-methoxyphenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound COC1=CC=CC(N2C(=CC(C)=N2)N2[C@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=C1 HSEMOQSMMUHGHR-IFMALSPDSA-N 0.000 claims description 3
- VFEMSVWYPSRFIO-IEBWSBKVSA-N (2r,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-methylpropyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)CN1N=C(C)C=C1N1[C@@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 VFEMSVWYPSRFIO-IEBWSBKVSA-N 0.000 claims description 3
- JFTZDOIFWCIKSV-FYYLOGMGSA-N (2r,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1C[C@H](CN1C1=CC(=NN1CCC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 JFTZDOIFWCIKSV-FYYLOGMGSA-N 0.000 claims description 3
- SAXXUFDIJRCLFF-CZUORRHYSA-N (2r,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CN=C1N1[C@@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)C1 SAXXUFDIJRCLFF-CZUORRHYSA-N 0.000 claims description 3
- JEIZTCMUVBAMTL-DZGCQCFKSA-N (2r,4s)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@@H](C(=O)NC2(CC2)C#N)C1 JEIZTCMUVBAMTL-DZGCQCFKSA-N 0.000 claims description 3
- SJOPCFIQTWRYAW-SGIRGMQISA-N (2r,4s,5r)-4-(benzenesulfonyl)-n-(1-cyanocyclopropyl)-5-(4-fluorophenyl)-2-(2-methylpropyl)pyrrolidine-2-carboxamide Chemical compound C1([C@@H]2[C@H](C[C@](N2)(CC(C)C)C(=O)NC2(CC2)C#N)S(=O)(=O)C=2C=CC=CC=2)=CC=C(F)C=C1 SJOPCFIQTWRYAW-SGIRGMQISA-N 0.000 claims description 3
- XCGZLWDQAQDHTK-IRLDBZIGSA-N (2s,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1CC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 XCGZLWDQAQDHTK-IRLDBZIGSA-N 0.000 claims description 3
- KJQBGHJLZQVCMT-AEFFLSMTSA-N (2s,4r)-1-(2-tert-butyl-5-methylpyrazol-3-yl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)(C)N1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 KJQBGHJLZQVCMT-AEFFLSMTSA-N 0.000 claims description 3
- BAEXLMXMACUHLN-WBVHZDCISA-N (2s,4r)-1-acetyl-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)Cl)NC1(C#N)CC1 BAEXLMXMACUHLN-WBVHZDCISA-N 0.000 claims description 3
- ZWGOEXKJPXSLSU-MJGOQNOKSA-N (2s,4r)-1-benzyl-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(CC=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 ZWGOEXKJPXSLSU-MJGOQNOKSA-N 0.000 claims description 3
- GPVHGMPPMPJXTK-GGAORHGYSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1CCC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 GPVHGMPPMPJXTK-GGAORHGYSA-N 0.000 claims description 3
- HNHKAJAJBZHVBM-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-(2-methoxyacetyl)pyrrolidine-2-carboxamide Chemical compound C1[C@@H](C(=O)NCC#N)N(C(=O)COC)C[C@@H]1S(=O)(=O)C1=CC=CC=C1Cl HNHKAJAJBZHVBM-YPMHNXCESA-N 0.000 claims description 3
- JASWMMAPJMJFDK-UXHICEINSA-N (2s,4r)-4-(benzenesulfonyl)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)S(=O)(=O)C=1C=CC=CC=1)NC1(C#N)CC1 JASWMMAPJMJFDK-UXHICEINSA-N 0.000 claims description 3
- LSNRQNOSWSWKBO-MSOLQXFVSA-N (2s,4r)-4-(benzenesulfonyl)-1-benzoyl-n-(cyanomethyl)pyrrolidine-2-carboxamide Chemical compound C([C@@H](C[C@H]1C(NCC#N)=O)S(=O)(=O)C=2C=CC=CC=2)N1C(=O)C1=CC=CC=C1 LSNRQNOSWSWKBO-MSOLQXFVSA-N 0.000 claims description 3
- SPZFBBAYXNSUJY-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclohexyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCCCC1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 SPZFBBAYXNSUJY-CTNGQTDRSA-N 0.000 claims description 3
- CXKHKXSDYBXIFC-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-2-phenylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 CXKHKXSDYBXIFC-CTNGQTDRSA-N 0.000 claims description 3
- XDVZGAQYHGPJSS-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-2-pyridazin-3-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1N=NC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 XDVZGAQYHGPJSS-AEFFLSMTSA-N 0.000 claims description 3
- VJPRLDAIZUFZIN-WBVHZDCISA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(1,3-thiazol-2-yl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1SC=CN=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 VJPRLDAIZUFZIN-WBVHZDCISA-N 0.000 claims description 3
- JFTZDOIFWCIKSV-GGAORHGYSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1CCC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 JFTZDOIFWCIKSV-GGAORHGYSA-N 0.000 claims description 3
- FEKYNIIMIZROIK-WBVHZDCISA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-cyclopropyl-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)C1CC1)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 FEKYNIIMIZROIK-WBVHZDCISA-N 0.000 claims description 3
- GRCGGEOZTFGSOW-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-pyrazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1N=CC=C1)NC1(C#N)CC1 GRCGGEOZTFGSOW-HIFRSBDPSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- 125000006430 alkyl cyclopropyl group Chemical group 0.000 claims description 3
- 125000006242 amine protecting group Chemical group 0.000 claims description 3
- 239000012351 deprotecting agent Substances 0.000 claims description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
- QZIZIEMLKOHQKD-MJGOQNOKSA-N methyl 4-[(2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carbonyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 QZIZIEMLKOHQKD-MJGOQNOKSA-N 0.000 claims description 3
- ICOJWNJOELOWSI-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-1-(oxan-4-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)C1CN(C2CCOCC2)C(C(=O)NC2(CC2)C#N)C1 ICOJWNJOELOWSI-UHFFFAOYSA-N 0.000 claims description 3
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- OWIJBDCOZFORRP-HIFRSBDPSA-N propan-2-yl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 OWIJBDCOZFORRP-HIFRSBDPSA-N 0.000 claims description 3
- UMMGZXWFUMYZAC-SJORKVTESA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,4-dimethylphenyl)sulfonylpyrrolidine-1-carboxylate Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(=O)NC2(CC2)C#N)C1 UMMGZXWFUMYZAC-SJORKVTESA-N 0.000 claims description 3
- VJUBYULIPGQGLQ-BPYOIECJSA-N tert-butyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[[cyano(phenyl)methyl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC(C#N)C1=CC=CC=C1 VJUBYULIPGQGLQ-BPYOIECJSA-N 0.000 claims description 3
- ZKXGYMUQFHRHPR-UHFFFAOYSA-N tert-butyl 4-[2-[(1-cyanocyclopropyl)carbamoyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(C(=O)NC2(CC2)C#N)CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 ZKXGYMUQFHRHPR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- OIIXHENHTKHBFP-TYZXPVIJSA-N (2R)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-N-(1-cyanocyclopropyl)-1-formylpyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)[C@@H]1N(CC(C1)S(=O)(=O)C1=C(C=C(C=C1)OCC(F)(F)F)Cl)C=O OIIXHENHTKHBFP-TYZXPVIJSA-N 0.000 claims description 2
- ASJJUKAMOSBGKI-FYYLOGMGSA-N (2r,4r)-1-[2-(3-acetamidophenyl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(=O)NC1=CC=CC(N2C(=CC(C)=N2)N2[C@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=C1 ASJJUKAMOSBGKI-FYYLOGMGSA-N 0.000 claims description 2
- HDSCZNUPELMQHT-YSVLISHTSA-N (2r,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(C)CC2)[C@@H](C(=O)NC2(CC2)C#N)C1 HDSCZNUPELMQHT-YSVLISHTSA-N 0.000 claims description 2
- DRDGLBWAZIDCCP-YSVLISHTSA-N (2r,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2-dimethylpropanoyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C(C)(C)C)[C@@H](C(=O)NC2(CC2)C#N)C1 DRDGLBWAZIDCCP-YSVLISHTSA-N 0.000 claims description 2
- HWENTYPXIQTUGX-XGWLTEMNSA-N (2r,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(cyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2CC2)[C@@H](C(=O)NC2(CC2)C#N)C1 HWENTYPXIQTUGX-XGWLTEMNSA-N 0.000 claims description 2
- ACDZAASPTGKUOL-JGGQBBKZSA-N (2r,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@@H](C(=O)NC2(CC2)C#N)C1 ACDZAASPTGKUOL-JGGQBBKZSA-N 0.000 claims description 2
- JAWKSAGTDLZHEH-IEBWSBKVSA-N (2r,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)N1N=C(C)C=C1N1[C@@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)C(F)(F)F)C1 JAWKSAGTDLZHEH-IEBWSBKVSA-N 0.000 claims description 2
- XTOCKLMEWOHIFG-KBXCAEBGSA-N (2r,4s)-1-(3-chloro-4-fluorophenyl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=C(Cl)C(F)=CC=C1N1[C@@H](C(=O)NC2(CC2)C#N)C[C@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 XTOCKLMEWOHIFG-KBXCAEBGSA-N 0.000 claims description 2
- JBFWXIQMBQQQLW-CABCVRRESA-N (2s,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-methylsulfonylpyrrolidine-2-carboxylic acid Chemical compound C=1C=CC=CC=1CN1N=C(C)C=C1N1C[C@H](S(C)(=O)=O)C[C@H]1C(O)=O JBFWXIQMBQQQLW-CABCVRRESA-N 0.000 claims description 2
- ORVLQKRKZUJCDG-OCCSQVGLSA-N (2s,4r)-1-acetyl-4-(2-chloro-4-fluorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC(F)=CC=1)Cl)NC1(C#N)CC1 ORVLQKRKZUJCDG-OCCSQVGLSA-N 0.000 claims description 2
- TVMZJVODJJLVJA-OCCSQVGLSA-N (2s,4r)-1-acetyl-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 TVMZJVODJJLVJA-OCCSQVGLSA-N 0.000 claims description 2
- DNJDPJDUSKMTMR-WBVHZDCISA-N (2s,4r)-1-acetyl-n-(1-cyanocyclopropyl)-4-[4-imidazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC(=CC=1)N1C=NC=C1)C(F)(F)F)NC1(C#N)CC1 DNJDPJDUSKMTMR-WBVHZDCISA-N 0.000 claims description 2
- YCQUEYPCUSMDMP-WBVHZDCISA-N (2s,4r)-1-acetyl-n-(1-cyanocyclopropyl)-4-[4-pyrazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)C(F)(F)F)NC1(C#N)CC1 YCQUEYPCUSMDMP-WBVHZDCISA-N 0.000 claims description 2
- YGKZGTBVPYJDID-MJGOQNOKSA-N (2s,4r)-4-(2-chloro-4-piperidin-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CCCCC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 YGKZGTBVPYJDID-MJGOQNOKSA-N 0.000 claims description 2
- JYZZYEBEONCNEC-WBVHZDCISA-N (2s,4r)-4-(2-chloro-4-piperidin-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1Cl)N1CCCCC1)NC1(C#N)CC1 JYZZYEBEONCNEC-WBVHZDCISA-N 0.000 claims description 2
- ISRLMROHSCSEGJ-OLZOCXBDSA-N (2s,4r)-4-(4-chloro-2-methylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound CC1=CC(Cl)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 ISRLMROHSCSEGJ-OLZOCXBDSA-N 0.000 claims description 2
- ZBTJPDCKQAMFSD-MOPGFXCFSA-N (2s,4r)-4-(benzenesulfonyl)-1-benzyl-n-(cyanomethyl)pyrrolidine-2-carboxamide Chemical compound C([C@@H](C[C@H]1C(NCC#N)=O)S(=O)(=O)C=2C=CC=CC=2)N1CC1=CC=CC=C1 ZBTJPDCKQAMFSD-MOPGFXCFSA-N 0.000 claims description 2
- LOSDTQRPLVMXMY-YADHBBJMSA-N (2s,4r)-4-(benzenesulfonyl)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)S(=O)(=O)C=1C=CC=CC=1)NC1(C#N)CC1 LOSDTQRPLVMXMY-YADHBBJMSA-N 0.000 claims description 2
- JEIZTCMUVBAMTL-HIFRSBDPSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 JEIZTCMUVBAMTL-HIFRSBDPSA-N 0.000 claims description 2
- RUGGRAFNUPWNGC-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCC1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 RUGGRAFNUPWNGC-MJGOQNOKSA-N 0.000 claims description 2
- LMHPEWUQJURZKH-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCC1)C)S(=O)(=O)C=1C(=CC(F)=CC=1)C(F)(F)F)NC1(C#N)CC1 LMHPEWUQJURZKH-MJGOQNOKSA-N 0.000 claims description 2
- SZZAXXFWMYBENB-CABCVRRESA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-methylsulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCC1)C)S(C)(=O)=O)NC1(C#N)CC1 SZZAXXFWMYBENB-CABCVRRESA-N 0.000 claims description 2
- RFXBTSWGBRTAFN-PBHICJAKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-cyclopropyl-1h-pyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C=2NN=C(C=2)C2CC2)[C@H](C(=O)NC2(CC2)C#N)C1 RFXBTSWGBRTAFN-PBHICJAKSA-N 0.000 claims description 2
- OSBBZVBCPFGKKD-DVECYGJZSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-2-quinolin-4-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C2=CC=CC=C2N=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 OSBBZVBCPFGKKD-DVECYGJZSA-N 0.000 claims description 2
- OZELYXTULCOLJH-MOPGFXCFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]-4-methylsulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1CCC=1C=CC=CC=1)C)S(C)(=O)=O)NC1(C#N)CC1 OZELYXTULCOLJH-MOPGFXCFSA-N 0.000 claims description 2
- LQTSRLUEPTWQPF-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-pyrimidin-2-yl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C=2N=CC=CN=2)[C@H](C(=O)NC2(CC2)C#N)C1 LQTSRLUEPTWQPF-HIFRSBDPSA-N 0.000 claims description 2
- HWQYXXCDGGYYAB-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(2,2-dimethylpropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)NC1(C#N)CC1 HWQYXXCDGGYYAB-HIFRSBDPSA-N 0.000 claims description 2
- IXHNIHNAMAIXKQ-KGLIPLIRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dimethylphenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 IXHNIHNAMAIXKQ-KGLIPLIRSA-N 0.000 claims description 2
- AWARAIMMIHGOLO-KGLIPLIRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(cyclopropylmethylsulfonyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)CC1CC1)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 AWARAIMMIHGOLO-KGLIPLIRSA-N 0.000 claims description 2
- IHFUGRIHVKQJGW-CABCVRRESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(cyclopropylmethylsulfonyl)-1-[5-methyl-2-(2,2,2-trifluoroethyl)pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)CN1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)CC2CC2)C1 IHFUGRIHVKQJGW-CABCVRRESA-N 0.000 claims description 2
- VGDYLBOATTXTMO-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-imidazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1C=NC=C1)NC1(C#N)CC1 VGDYLBOATTXTMO-HIFRSBDPSA-N 0.000 claims description 2
- NXTHIWLNTWKUBS-ZBFHGGJFSA-N (2s,4r)-n-(cyanomethyl)-1-(oxane-4-carbonyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2CCOCC2)[C@H](C(=O)NCC#N)C1 NXTHIWLNTWKUBS-ZBFHGGJFSA-N 0.000 claims description 2
- GVUPCWCOWHNOHV-UHFFFAOYSA-N 1-aminocyclobutane-1-carbonitrile Chemical compound N#CC1(N)CCC1 GVUPCWCOWHNOHV-UHFFFAOYSA-N 0.000 claims description 2
- HUMMCZRNZCKXHL-UHFFFAOYSA-N 1-aminocyclohexane-1-carbonitrile Chemical compound N#CC1(N)CCCCC1 HUMMCZRNZCKXHL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000006323 alkenyl amino group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000004188 dichlorophenyl group Chemical group 0.000 claims description 2
- DWFMMHPLDQBUEW-OCCSQVGLSA-N ethyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OCC)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 DWFMMHPLDQBUEW-OCCSQVGLSA-N 0.000 claims description 2
- 125000004992 haloalkylamino group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- XFCXNEUWSKNAGE-AEFFLSMTSA-N methyl 4-[(2s,4r)-2-(cyanomethylcarbamoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carbonyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(=O)N1[C@H](C(=O)NCC#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 XFCXNEUWSKNAGE-AEFFLSMTSA-N 0.000 claims description 2
- 125000006542 morpholinylalkyl group Chemical group 0.000 claims description 2
- FVYOGMAUYRNGCY-UHFFFAOYSA-N n-(1-cyanocyclopropyl)-1-[3-(trifluoromethoxy)phenyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)OC1=CC=CC(N2C(CC(C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=C1 FVYOGMAUYRNGCY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- KJQNCXKSSGYQRR-WZOHSFFVSA-N tert-butyl (2r,4s,5r)-2-[(1-cyanocyclopropyl)carbamoyl]-5-(4-fluorophenyl)-2-(2-methylpropyl)-4-methylsulfonylpyrrolidine-1-carboxylate Chemical compound C1([C@@H]2[C@H](C[C@](N2C(=O)OC(C)(C)C)(CC(C)C)C(=O)NC2(CC2)C#N)S(C)(=O)=O)=CC=C(F)C=C1 KJQNCXKSSGYQRR-WZOHSFFVSA-N 0.000 claims description 2
- CCPXGOKXNRIJJP-RZCQNPAPSA-N tert-butyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyano-1-phenylethyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC(C)(C#N)C1=CC=CC=C1 CCPXGOKXNRIJJP-RZCQNPAPSA-N 0.000 claims description 2
- JJLJRPASVQJKMC-CVEARBPZSA-N tert-butyl (2s,4r)-4-(4-chloro-2-methylphenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound CC1=CC(Cl)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(=O)NC2(CC2)C#N)C1 JJLJRPASVQJKMC-CVEARBPZSA-N 0.000 claims description 2
- LLRSJNZNMMDXOX-AEFFLSMTSA-N tert-butyl n-[1-[(2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carbonyl]cyclopropyl]carbamate Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(NC(=O)OC(C)(C)C)CC1 LLRSJNZNMMDXOX-AEFFLSMTSA-N 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- XQJSWXOEXOSLBS-VGAJERRHSA-N (2R)-4-[2-chloro-4-(2-methoxyethoxy)phenyl]sulfonyl-1-[1-(6-chloropyridin-3-yl)cyclopropanecarbonyl]-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)[C@@H]1N(CC(C1)S(=O)(=O)C1=C(C=C(C=C1)OCCOC)Cl)C(=O)C1(CC1)C=1C=NC(=CC1)Cl XQJSWXOEXOSLBS-VGAJERRHSA-N 0.000 claims 1
- YJNYCMPTHYQPIA-GGAORHGYSA-N (2s,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-(2-chloro-4-methoxyphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OC)=CC=C1S(=O)(=O)[C@H]1CN(C=2N(N=C(C)C=2)CC=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 YJNYCMPTHYQPIA-GGAORHGYSA-N 0.000 claims 1
- DTKFTFRIWGPVEO-ZZNRJTPNSA-N (2s,4r)-1-[2-(4-chlorophenyl)-2-morpholin-4-ylacetyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C(C(=O)N1[C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC=CC=1)Cl)C(=O)NC1(CC1)C#N)N1CCOCC1 DTKFTFRIWGPVEO-ZZNRJTPNSA-N 0.000 claims 1
- JJRBNQZMCNJFNT-UMFITKPXSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-[cyano(phenyl)methyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC(C#N)C=2C=CC=CC=2)NC1 JJRBNQZMCNJFNT-UMFITKPXSA-N 0.000 claims 1
- JOEAKDHZVYRUNI-IRLDBZIGSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-[4-pyrazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCC1)C)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)C(F)(F)F)NC1(C#N)CC1 JOEAKDHZVYRUNI-IRLDBZIGSA-N 0.000 claims 1
- JYXBQAIFJKMXKO-OFNKIYASSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-[4-pyrimidin-4-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCC1)C)S(=O)(=O)C=1C(=CC(=CC=1)C=1N=CN=CC=1)C(F)(F)F)NC1(C#N)CC1 JYXBQAIFJKMXKO-OFNKIYASSA-N 0.000 claims 1
- OFGJTLKIYOMWEY-KGLIPLIRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2-ethylphenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound CCC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 OFGJTLKIYOMWEY-KGLIPLIRSA-N 0.000 claims 1
- HCPRFDRBZDRUOB-OLZOCXBDSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(hydroxymethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound OCC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 HCPRFDRBZDRUOB-OLZOCXBDSA-N 0.000 claims 1
- IECVIKWDVAGBBO-MNOVXSKESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethoxy)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)OC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 IECVIKWDVAGBBO-MNOVXSKESA-N 0.000 claims 1
- OWTKXURHYHLZLF-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-morpholin-4-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1CCOCC1)NC1(C#N)CC1 OWTKXURHYHLZLF-ZBFHGGJFSA-N 0.000 claims 1
- MTKBHIBTALLJEK-UHFFFAOYSA-N 1-(methylamino)cyclopropane-1-carbonitrile Chemical compound CNC1(C#N)CC1 MTKBHIBTALLJEK-UHFFFAOYSA-N 0.000 claims 1
- JQULXIOYDDCNGR-UHFFFAOYSA-N 2-amino-2-methylpropanenitrile Chemical compound CC(C)(N)C#N JQULXIOYDDCNGR-UHFFFAOYSA-N 0.000 claims 1
- ZXIXBPGNGUZOBB-UHFFFAOYSA-N 2-amino-2-phenylpropanenitrile Chemical compound N#CC(N)(C)C1=CC=CC=C1 ZXIXBPGNGUZOBB-UHFFFAOYSA-N 0.000 claims 1
- LUPJHNFDSXJOEE-UHFFFAOYSA-N 4-(benzenesulfonyl)-5-(4-tert-butylphenyl)-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C1C(S(=O)(=O)C=2C=CC=CC=2)CC(C(=O)NC2(CC2)C#N)N1 LUPJHNFDSXJOEE-UHFFFAOYSA-N 0.000 claims 1
- NNBWDNIAIQEUSP-UHFFFAOYSA-N N-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)C1N(CCC1)C(=O)C1(CC1)C(F)(F)F NNBWDNIAIQEUSP-UHFFFAOYSA-N 0.000 claims 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims 1
- PUHBBXDIFAZMJE-UNWVZKJWSA-N tert-butyl n-[(1r)-1-(4-chlorophenyl)-2-[(2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]carbamate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@H](NC(=O)OC(C)(C)C)C=1C=CC(Cl)=CC=1)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 PUHBBXDIFAZMJE-UNWVZKJWSA-N 0.000 claims 1
- BXTMLOAYHZHOKI-UVSGPOQTSA-N tert-butyl n-[4-[2-[(2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]cyclohexyl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCC1CC(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C1 BXTMLOAYHZHOKI-UVSGPOQTSA-N 0.000 claims 1
- 239000007787 solid Substances 0.000 description 277
- 238000002474 experimental method Methods 0.000 description 222
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
- 239000000203 mixture Substances 0.000 description 154
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 146
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- 239000000243 solution Substances 0.000 description 111
- 239000011541 reaction mixture Substances 0.000 description 104
- PCEIEQLJYDMRFZ-UHFFFAOYSA-N (1-cyanocyclopropyl)azanium;chloride Chemical compound Cl.N#CC1(N)CC1 PCEIEQLJYDMRFZ-UHFFFAOYSA-N 0.000 description 100
- 239000000460 chlorine Substances 0.000 description 99
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 92
- 239000007858 starting material Substances 0.000 description 90
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
- 239000012230 colorless oil Substances 0.000 description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 75
- 239000003921 oil Substances 0.000 description 73
- 235000019198 oils Nutrition 0.000 description 73
- 239000007821 HATU Substances 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- 239000006260 foam Substances 0.000 description 60
- 238000000746 purification Methods 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 55
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 53
- 235000019439 ethyl acetate Nutrition 0.000 description 52
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
- 229940093499 ethyl acetate Drugs 0.000 description 47
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- 239000011734 sodium Substances 0.000 description 44
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 43
- 239000012044 organic layer Substances 0.000 description 43
- 239000002253 acid Substances 0.000 description 41
- 239000012267 brine Substances 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 38
- 238000010511 deprotection reaction Methods 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 35
- 229910002027 silica gel Inorganic materials 0.000 description 35
- 229960001866 silicon dioxide Drugs 0.000 description 35
- 238000005859 coupling reaction Methods 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 230000008878 coupling Effects 0.000 description 32
- 238000010168 coupling process Methods 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 32
- 239000002585 base Substances 0.000 description 31
- 239000010410 layer Substances 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 238000002953 preparative HPLC Methods 0.000 description 29
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 150000003457 sulfones Chemical class 0.000 description 26
- 150000003568 thioethers Chemical class 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- ZOPZIRRUJQAXEA-IYJPBCIQSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 ZOPZIRRUJQAXEA-IYJPBCIQSA-N 0.000 description 24
- 239000000463 material Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 21
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 19
- 150000001408 amides Chemical class 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 230000003647 oxidation Effects 0.000 description 18
- 238000007254 oxidation reaction Methods 0.000 description 18
- 108090000613 Cathepsin S Proteins 0.000 description 17
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 17
- 102100035654 Cathepsin S Human genes 0.000 description 16
- 239000006227 byproduct Substances 0.000 description 16
- 150000002825 nitriles Chemical class 0.000 description 16
- 150000007513 acids Chemical class 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 14
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 14
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 14
- 239000005457 ice water Substances 0.000 description 14
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 14
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 13
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 13
- 235000019502 Orange oil Nutrition 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000012458 free base Substances 0.000 description 13
- 239000010502 orange oil Substances 0.000 description 13
- AAOHZWPZUYGKRQ-IYJPBCIQSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 AAOHZWPZUYGKRQ-IYJPBCIQSA-N 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 10
- CLCBKHICKFJHAH-UHFFFAOYSA-N N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C(NC1(CC1)C#N)C1CCCN1 CLCBKHICKFJHAH-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 239000012317 TBTU Substances 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- DBNLGTYGKCMLLR-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]hydrazine Chemical compound NNC1=CC=C(C(F)(F)F)C=C1 DBNLGTYGKCMLLR-UHFFFAOYSA-N 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 9
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 9
- 229940067157 phenylhydrazine Drugs 0.000 description 9
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 9
- 235000013930 proline Nutrition 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- PCHMIPHJGUTFKQ-XQKZEKTMSA-N (2s,4r)-n-(cyanomethyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NCC#N)NC1 PCHMIPHJGUTFKQ-XQKZEKTMSA-N 0.000 description 8
- WWODHWXIRZEIFO-UHFFFAOYSA-N 1-ethenylsulfonyl-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)C=C WWODHWXIRZEIFO-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 150000008361 aminoacetonitriles Chemical class 0.000 description 8
- 150000008064 anhydrides Chemical class 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- AYLGWQSBYBGCJQ-XQKZEKTMSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NCC#N)NC1 AYLGWQSBYBGCJQ-XQKZEKTMSA-N 0.000 description 7
- 229930040373 Paraformaldehyde Natural products 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- ZHIXOIFQJGTWMY-YPMHNXCESA-N methyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-(3-oxobutanethioyl)pyrrolidine-2-carboxylate Chemical compound C1N(C(=S)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl ZHIXOIFQJGTWMY-YPMHNXCESA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229920002866 paraformaldehyde Polymers 0.000 description 7
- 150000003148 prolines Chemical class 0.000 description 7
- 238000007127 saponification reaction Methods 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- YCFQPRVUXPTFON-UHFFFAOYSA-N (2-chloropyridin-4-yl)hydrazine Chemical compound NNC1=CC=NC(Cl)=C1 YCFQPRVUXPTFON-UHFFFAOYSA-N 0.000 description 6
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- 239000005711 Benzoic acid Substances 0.000 description 6
- 108090000624 Cathepsin L Proteins 0.000 description 6
- 102000004172 Cathepsin L Human genes 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 235000010233 benzoic acid Nutrition 0.000 description 6
- 208000020832 chronic kidney disease Diseases 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000012746 preparative thin layer chromatography Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 6
- XVGQHRKNXSUPEF-UHFFFAOYSA-N 2-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=CC=C1S XVGQHRKNXSUPEF-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 230000007211 cardiovascular event Effects 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- JKUYRAMKJLMYLO-UHFFFAOYSA-N tert-butyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OC(C)(C)C JKUYRAMKJLMYLO-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- QPROXFPLXMRMIY-IEBWSBKVSA-N (2r,4r)-1-[2-(3-methoxyphenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound COC1=CC=CC(N2C(=CC(C)=N2)N2[C@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(O)=O)=C1 QPROXFPLXMRMIY-IEBWSBKVSA-N 0.000 description 4
- PPCDJQFKROKEEC-UYAOXDASSA-N (2r,4r)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@H](C1)C(O)=O)C1=CC(=NN1CCC=1C=CC=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F PPCDJQFKROKEEC-UYAOXDASSA-N 0.000 description 4
- ZYMILHFJWXHWMK-LYCTWNKOSA-N (2s,4r)-4-(benzenesulfonyl)-n-(cyanomethyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.C1N[C@H](C(NCC#N)=O)C[C@H]1S(=O)(=O)C1=CC=CC=C1 ZYMILHFJWXHWMK-LYCTWNKOSA-N 0.000 description 4
- DQPQHEUELUTNQM-HIFRSBDPSA-N (2s,4r)-4-[4-bromo-2-(trifluoromethyl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(Br)=CC=1)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 DQPQHEUELUTNQM-HIFRSBDPSA-N 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- ISWHAFUPOKQVJB-YPMHNXCESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(F)C=C1C(F)(F)F ISWHAFUPOKQVJB-YPMHNXCESA-N 0.000 description 4
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 4
- MWWNNNAOGWPTQY-UHFFFAOYSA-N 3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(S(Cl)(=O)=O)=C1 MWWNNNAOGWPTQY-UHFFFAOYSA-N 0.000 description 4
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- AQOZZSWECZTDNR-UHFFFAOYSA-N cyclobutylhydrazine;hydrochloride Chemical compound Cl.NNC1CCC1 AQOZZSWECZTDNR-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- ILULYDJFTJKQAP-UHFFFAOYSA-N hydron;propan-2-ylhydrazine;chloride Chemical compound [Cl-].CC(C)N[NH3+] ILULYDJFTJKQAP-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- BUCDGDQPMBNHIR-DGCLKSJQSA-N methyl (2r,4r)-1-(3-oxobutanethioyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C(=S)CC(C)=O)[C@@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F BUCDGDQPMBNHIR-DGCLKSJQSA-N 0.000 description 4
- AKRYBBWYDSDZHG-UHFFFAOYSA-N nitrosobis(2-oxopropyl)amine Chemical compound CC(=O)CN(N=O)CC(C)=O AKRYBBWYDSDZHG-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- QHUIJQPQVQVPJW-IEBWSBKVSA-N (2r,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@H](C1)C(O)=O)C1=CC(=NN1CC=1C=CC=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F QHUIJQPQVQVPJW-IEBWSBKVSA-N 0.000 description 3
- GCCCKOBXXMITIR-SJLPKXTDSA-N (2r,4r)-1-(2-cyclohexyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@H](C1)C(O)=O)C1=CC(=NN1C1CCCCC1)C)(=O)C1=CC=CC=C1C(F)(F)F GCCCKOBXXMITIR-SJLPKXTDSA-N 0.000 description 3
- NKYLBKILKJLJGF-GDBMZVCRSA-N (2r,4r)-1-[5-methyl-2-(2-methylpropyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CC(C)CN1N=C(C)C=C1N1[C@@H](C(O)=O)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 NKYLBKILKJLJGF-GDBMZVCRSA-N 0.000 description 3
- ZPBIYZHGBPBZCK-VKHMYHEASA-N (2s)-4,4-difluoropyrrolidin-1-ium-2-carboxylate Chemical compound OC(=O)[C@@H]1CC(F)(F)CN1 ZPBIYZHGBPBZCK-VKHMYHEASA-N 0.000 description 3
- MBSITGGDZGCVCS-OCCSQVGLSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(3,3,3-trifluoropropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CCC(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 MBSITGGDZGCVCS-OCCSQVGLSA-N 0.000 description 3
- LVQLUOFXJVYSHM-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-formylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C=O)[C@H](C(=O)NC2(CC2)C#N)C1 LVQLUOFXJVYSHM-YPMHNXCESA-N 0.000 description 3
- UPZCIFMMHVEQJD-OCCSQVGLSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-n,1-dimethylpyrrolidine-2-carboxamide Chemical compound O=S([C@@H]1C[C@H](N(C1)C)C(=O)N(C)C1(CC1)C#N)(=O)C1=CC=CC=C1Cl UPZCIFMMHVEQJD-OCCSQVGLSA-N 0.000 description 3
- UQYDSZAUEPLSEQ-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2,5-dimethylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CN1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 UQYDSZAUEPLSEQ-ZBFHGGJFSA-N 0.000 description 3
- PZKUXAGPXAZLAN-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(4-fluorobenzoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=CC(F)=CC=C1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 PZKUXAGPXAZLAN-AEFFLSMTSA-N 0.000 description 3
- QLZWVGOIFUBJQZ-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-1h-pyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound N1C(C)=CC(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=N1 QLZWVGOIFUBJQZ-HIFRSBDPSA-N 0.000 description 3
- WBCGQQSVFAYKMS-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-methylpyridin-4-yl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(C)N=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 WBCGQQSVFAYKMS-CTNGQTDRSA-N 0.000 description 3
- YFIWJGMOPHYNJC-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)S(=O)(=O)C=1C(=CC(F)=CC=1)C(F)(F)F)NC1(C#N)CC1 YFIWJGMOPHYNJC-CTNGQTDRSA-N 0.000 description 3
- NSNOPBMFPAKWGD-PBCQUBLHSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-imidazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1C=NC=C1)NC1(C#N)CC1 NSNOPBMFPAKWGD-PBCQUBLHSA-N 0.000 description 3
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 3
- MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 description 3
- SKCBKBCACWDALV-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C(F)(F)F)CC1 SKCBKBCACWDALV-UHFFFAOYSA-N 0.000 description 3
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 3
- JDJNSFSTSJWJFA-UHFFFAOYSA-N 1-cyclopropylpiperazine;dihydrochloride Chemical compound Cl.Cl.C1CC1N1CCNCC1 JDJNSFSTSJWJFA-UHFFFAOYSA-N 0.000 description 3
- QXXHHHWXFHPNOS-UHFFFAOYSA-N 1-phenylcyclohexane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CCCCC1 QXXHHHWXFHPNOS-UHFFFAOYSA-N 0.000 description 3
- IWWCCNVRNHTGLV-UHFFFAOYSA-N 1-phenylcyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CC1 IWWCCNVRNHTGLV-UHFFFAOYSA-N 0.000 description 3
- FGBVJFREPSJSNG-UHFFFAOYSA-N 2,4-dichlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1Cl FGBVJFREPSJSNG-UHFFFAOYSA-N 0.000 description 3
- VSYBJHJIBPLSCJ-UHFFFAOYSA-N 2-(4-bromophenyl)-1,3-dioxolane-2-carboxylic acid Chemical compound C=1C=C(Br)C=CC=1C1(C(=O)O)OCCO1 VSYBJHJIBPLSCJ-UHFFFAOYSA-N 0.000 description 3
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 3
- UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 3
- 235000013405 beer Nutrition 0.000 description 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- PMMYEEVYMWASQN-IMJSIDKUSA-N cis-4-Hydroxy-L-proline Chemical class O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 229910003002 lithium salt Inorganic materials 0.000 description 3
- 159000000002 lithium salts Chemical class 0.000 description 3
- SGNBAXPADSYIBL-DGCLKSJQSA-N methyl (2r,4r)-1-(3-oxobutanoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C(=O)CC(C)=O)[C@@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F SGNBAXPADSYIBL-DGCLKSJQSA-N 0.000 description 3
- VCGCNMWUZAPYQS-SCZZXKLOSA-N methyl (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F VCGCNMWUZAPYQS-SCZZXKLOSA-N 0.000 description 3
- NNJGJXXQTFLDNE-YPMHNXCESA-N methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-(3-oxobutanoyl)pyrrolidine-2-carboxylate Chemical compound C1N(C(=O)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(F)C=C1C(F)(F)F NNJGJXXQTFLDNE-YPMHNXCESA-N 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- WOSKZEUXIRAPHD-LXZKKBNFSA-N tert-butyl (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(=O)NC2(CC2)C#N)C1 WOSKZEUXIRAPHD-LXZKKBNFSA-N 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- YAJMVNAZFUCHBP-WHCXFUJUSA-N (2R)-4-[2-chloro-4-(4-methylpiperazin-1-yl)phenyl]sulfonyl-N-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)[C@@H]1N(CC(C1)S(=O)(=O)C1=C(C=C(C=C1)N1CCN(CC1)C)Cl)C(=O)C1(CC1)C(F)(F)F YAJMVNAZFUCHBP-WHCXFUJUSA-N 0.000 description 2
- QQVMSLOWHJMSPZ-GDBMZVCRSA-N (2r,4r)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@H](C1)C(O)=O)C1=CC(=NN1C1CCC1)C)(=O)C1=CC=CC=C1C(F)(F)F QQVMSLOWHJMSPZ-GDBMZVCRSA-N 0.000 description 2
- CJISTOZCYHOAPO-UYAOXDASSA-N (2r,4r)-1-[2-(3-acetamidophenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CC(=O)NC1=CC=CC(N2C(=CC(C)=N2)N2[C@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(O)=O)=C1 CJISTOZCYHOAPO-UYAOXDASSA-N 0.000 description 2
- QHUIJQPQVQVPJW-MJGOQNOKSA-N (2s,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1CC=1C=CC=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F QHUIJQPQVQVPJW-MJGOQNOKSA-N 0.000 description 2
- JLMBWILICTWELD-CTNGQTDRSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclobutanecarbonyl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CCC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 JLMBWILICTWELD-CTNGQTDRSA-N 0.000 description 2
- ZRFVVHNZYJPPNV-GGAORHGYSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopentanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CCCC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 ZRFVVHNZYJPPNV-GGAORHGYSA-N 0.000 description 2
- CJISTOZCYHOAPO-QUCCMNQESA-N (2s,4r)-1-[2-(3-acetamidophenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CC(=O)NC1=CC=CC(N2C(=CC(C)=N2)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(O)=O)=C1 CJISTOZCYHOAPO-QUCCMNQESA-N 0.000 description 2
- ZLMFWSNLCRAZOD-CTNGQTDRSA-N (2s,4r)-1-[2-(3-chlorophenyl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(Cl)C=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 ZLMFWSNLCRAZOD-CTNGQTDRSA-N 0.000 description 2
- OXJCJCAVNOKVMH-WJTCQHJGSA-N (2s,4r)-1-[2-(4-acetamidocyclohexyl)acetyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CC(NC(=O)C)CCC1CC(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C1 OXJCJCAVNOKVMH-WJTCQHJGSA-N 0.000 description 2
- NGGNHVXUDAJQLN-CTNGQTDRSA-N (2s,4r)-1-[2-(4-bromophenyl)-1,3-dioxolane-2-carbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(OCCO2)C=2C=CC(Br)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 NGGNHVXUDAJQLN-CTNGQTDRSA-N 0.000 description 2
- WOZGWTXSRXHPOK-CTNGQTDRSA-N (2s,4r)-1-[2-(4-chlorophenyl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(Cl)=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 WOZGWTXSRXHPOK-CTNGQTDRSA-N 0.000 description 2
- KMFTVTLGIKSYMJ-XLIONFOSSA-N (2s,4r)-1-[5-cyclopropyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C[C@H]1C(=O)O)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C2CC2)=NN1C1=CC=C(C(F)(F)F)C=C1 KMFTVTLGIKSYMJ-XLIONFOSSA-N 0.000 description 2
- NKYLBKILKJLJGF-ZBFHGGJFSA-N (2s,4r)-1-[5-methyl-2-(2-methylpropyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CC(C)CN1N=C(C)C=C1N1[C@H](C(O)=O)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 NKYLBKILKJLJGF-ZBFHGGJFSA-N 0.000 description 2
- PPCDJQFKROKEEC-QUCCMNQESA-N (2s,4r)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1CCC=1C=CC=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F PPCDJQFKROKEEC-QUCCMNQESA-N 0.000 description 2
- REEFZJNYQZRWLB-WBVHZDCISA-N (2s,4r)-1-benzoyl-n-(cyanomethyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C=2C=CC=CC=2)[C@H](C(=O)NCC#N)C1 REEFZJNYQZRWLB-WBVHZDCISA-N 0.000 description 2
- XCDMWFIWUZLLAJ-QUCCMNQESA-N (2s,4r)-4-(2-chloro-4-fluorophenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 XCDMWFIWUZLLAJ-QUCCMNQESA-N 0.000 description 2
- VIHONDQHUOTRJC-PWSUYJOCSA-N (2s,4r)-4-(2-chloro-4-fluorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 VIHONDQHUOTRJC-PWSUYJOCSA-N 0.000 description 2
- XNZPDLHTIXKNJI-WBVHZDCISA-N (2s,4r)-4-(2-chloro-4-piperidin-1-ylphenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1CCCCC1)Cl)NC1(C#N)CC1 XNZPDLHTIXKNJI-WBVHZDCISA-N 0.000 description 2
- RYXVSKALQCIQNK-AEFFLSMTSA-N (2s,4r)-4-(2-chloro-4-piperidin-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-formylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C=O)S(=O)(=O)C1=CC=C(C=C1Cl)N1CCCCC1)NC1(C#N)CC1 RYXVSKALQCIQNK-AEFFLSMTSA-N 0.000 description 2
- BOELYJZHIQNQCW-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-(4-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)Cl)C1 BOELYJZHIQNQCW-AEFFLSMTSA-N 0.000 description 2
- NMKNCLKFIPTZNR-MJGOQNOKSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 NMKNCLKFIPTZNR-MJGOQNOKSA-N 0.000 description 2
- JIEDAWLJJKXIRJ-YLAFAASESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclobutyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CCC2)C#N)NC1 JIEDAWLJJKXIRJ-YLAFAASESA-N 0.000 description 2
- GVGCALOSDZRRML-PBCQUBLHSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclohexyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CCCCC2)C#N)NC1 GVGCALOSDZRRML-PBCQUBLHSA-N 0.000 description 2
- KYRUHVSBTTZABG-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylpiperidine-4-carbonyl)pyrrolidine-2-carboxamide Chemical compound C1CN(C)CCC1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)Cl)C1 KYRUHVSBTTZABG-AEFFLSMTSA-N 0.000 description 2
- MJRJTBMNENNMLI-QUCCMNQESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(1-phenylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 MJRJTBMNENNMLI-QUCCMNQESA-N 0.000 description 2
- IZJVANWLBQMXLZ-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2,2-trifluoroethyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CC(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 IZJVANWLBQMXLZ-YPMHNXCESA-N 0.000 description 2
- LZJAUSWTAYXHEI-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2,3,3,3-pentafluoropropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CC(F)(F)C(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 LZJAUSWTAYXHEI-YPMHNXCESA-N 0.000 description 2
- VRWOWEBUCMZJHN-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2-difluoroethyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CC(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 VRWOWEBUCMZJHN-YPMHNXCESA-N 0.000 description 2
- XAGIRMMUDMVIFW-MJGOQNOKSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCC1)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 XAGIRMMUDMVIFW-MJGOQNOKSA-N 0.000 description 2
- IKWUHTOZNXPPIY-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(4-fluorobenzoyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(F)=CC=C1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)Cl)C1 IKWUHTOZNXPPIY-AEFFLSMTSA-N 0.000 description 2
- QYWBYOUPJJHDLF-QUCCMNQESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-[4-(trifluoromethoxy)phenyl]cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 QYWBYOUPJJHDLF-QUCCMNQESA-N 0.000 description 2
- OIJAKVSWDMMLHG-CTNGQTDRSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 OIJAKVSWDMMLHG-CTNGQTDRSA-N 0.000 description 2
- PWPRGHZVYYSWOZ-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-cyclohexylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C2CCCCC2)[C@H](C(=O)NC2(CC2)C#N)C1 PWPRGHZVYYSWOZ-AEFFLSMTSA-N 0.000 description 2
- CPXRHUJSGZDSNI-OCCSQVGLSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-ethylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CC)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 CPXRHUJSGZDSNI-OCCSQVGLSA-N 0.000 description 2
- SOACAOYPAWVNFU-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-methylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 SOACAOYPAWVNFU-YPMHNXCESA-N 0.000 description 2
- RDILZQBGOPNJQL-IYJPBCIQSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(2-cyanopropan-2-yl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.C1N[C@H](C(=O)NC(C)(C)C#N)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl RDILZQBGOPNJQL-IYJPBCIQSA-N 0.000 description 2
- KFIAQWAUIRKWHK-GIAWROPOSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-(2,2,2-trifluoro-1-phenylethyl)pyrrolidine-2-carboxamide Chemical compound O=S([C@H]1CN([C@@H](C1)C(=O)NCC#N)C(C(F)(F)F)C=1C=CC=CC=1)(=O)C1=CC=CC=C1Cl KFIAQWAUIRKWHK-GIAWROPOSA-N 0.000 description 2
- KNSMFAUYKPYKSS-WBVHZDCISA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-(cyclohexanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2CCCCC2)[C@H](C(=O)NCC#N)C1 KNSMFAUYKPYKSS-WBVHZDCISA-N 0.000 description 2
- SRJSSJAGBGASKJ-ZBFHGGJFSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-(oxan-4-yl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C2CCOCC2)[C@H](C(=O)NCC#N)C1 SRJSSJAGBGASKJ-ZBFHGGJFSA-N 0.000 description 2
- QWSTZPUTANJWMP-OCCSQVGLSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-(oxetan-3-yl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C2COC2)[C@H](C(=O)NCC#N)C1 QWSTZPUTANJWMP-OCCSQVGLSA-N 0.000 description 2
- SNIRKCSCDAWCJO-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-propanoylpyrrolidine-2-carboxamide Chemical compound C1[C@@H](C(=O)NCC#N)N(C(=O)CC)C[C@@H]1S(=O)(=O)C1=CC=CC=C1Cl SNIRKCSCDAWCJO-YPMHNXCESA-N 0.000 description 2
- BTTCZRBGQQSPMX-KZCZEQIWSA-N (2s,4r)-4-(4-chloro-2-methylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.CC1=CC(Cl)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 BTTCZRBGQQSPMX-KZCZEQIWSA-N 0.000 description 2
- KJXOTTFPWKDHKV-MOPGFXCFSA-N (2s,4r)-4-(benzenesulfonyl)-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)(=O)C1=CC=CC=C1 KJXOTTFPWKDHKV-MOPGFXCFSA-N 0.000 description 2
- QPFQLSLZNYYLMR-MOPGFXCFSA-N (2s,4r)-4-(benzenesulfonyl)-1-benzoyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@H]1N(C[C@@H](C1)S(=O)(=O)C=1C=CC=CC=1)C(=O)C=1C=CC=CC=1)NC1(C#N)CC1 QPFQLSLZNYYLMR-MOPGFXCFSA-N 0.000 description 2
- MKPLTLUASPIMBS-MSOLQXFVSA-N (2s,4r)-4-(benzenesulfonyl)-n-(1-cyanocyclopropyl)-1-(oxane-4-carbonyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@H]1N(C[C@@H](C1)S(=O)(=O)C=1C=CC=CC=1)C(=O)C1CCOCC1)NC1(C#N)CC1 MKPLTLUASPIMBS-MSOLQXFVSA-N 0.000 description 2
- SWCFBPTWVNNWSC-KZCZEQIWSA-N (2s,4r)-4-(benzenesulfonyl)-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C=1C=CC=CC=1)NC1(C#N)CC1 SWCFBPTWVNNWSC-KZCZEQIWSA-N 0.000 description 2
- FFSDEIPVWPWPEE-YTYFACEESA-N (2s,4r)-4-(benzenesulfonyl)-n-(cyanomethyl)-1-(2,2,2-trifluoro-1-phenylethyl)pyrrolidine-2-carboxamide Chemical compound O=S([C@H]1CN([C@@H](C1)C(=O)NCC#N)C(C(F)(F)F)C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FFSDEIPVWPWPEE-YTYFACEESA-N 0.000 description 2
- IZGBESPAUOUFFV-MSOLQXFVSA-N (2s,4r)-4-(benzenesulfonyl)-n-(cyanomethyl)-1-(cyclohexanecarbonyl)pyrrolidine-2-carboxamide Chemical compound C([C@@H](C[C@H]1C(NCC#N)=O)S(=O)(=O)C=2C=CC=CC=2)N1C(=O)C1CCCCC1 IZGBESPAUOUFFV-MSOLQXFVSA-N 0.000 description 2
- AJQYUSGWBOVLHG-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 AJQYUSGWBOVLHG-ZBFHGGJFSA-N 0.000 description 2
- WBMGUEVLQXYRPB-QUCCMNQESA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-pyridin-4-ylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CN=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 WBMGUEVLQXYRPB-QUCCMNQESA-N 0.000 description 2
- MQIASAKHXCJOJF-WBVHZDCISA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(3-methylbutanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC(C)C)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)NC1(C#N)CC1 MQIASAKHXCJOJF-WBVHZDCISA-N 0.000 description 2
- IHLXPRLZFAPTIS-AEFFLSMTSA-N (2s,4r)-4-[2-chloro-4-(4,4-difluoropiperidin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CCC(F)(F)CC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 IHLXPRLZFAPTIS-AEFFLSMTSA-N 0.000 description 2
- OYWHPRGLRHQYKZ-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(4,4-difluoropiperidin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CC(F)(F)CCN1C1=CC=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(Cl)=C1 OYWHPRGLRHQYKZ-ZBFHGGJFSA-N 0.000 description 2
- RYOCBXVXEXOWKM-QUCCMNQESA-N (2s,4r)-4-[2-chloro-4-(4-ethylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(CC)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 RYOCBXVXEXOWKM-QUCCMNQESA-N 0.000 description 2
- CZCVHOZGJZYVFQ-KNQAVFIVSA-N (2s,4r)-4-[2-chloro-4-(4-ethylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound C1CN(CC)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C=2C(=CC=CN=2)C(F)(F)F)C(Cl)=C1 CZCVHOZGJZYVFQ-KNQAVFIVSA-N 0.000 description 2
- ACDZAASPTGKUOL-BJJXKVORSA-N (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 ACDZAASPTGKUOL-BJJXKVORSA-N 0.000 description 2
- QOXLZGXUAPRKTK-SUHUHFCYSA-N (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 QOXLZGXUAPRKTK-SUHUHFCYSA-N 0.000 description 2
- CIAFWUFOTHQPJN-VPUSJEBWSA-N (2s,4r)-4-[4-(4-tert-butylpiperazin-1-yl)-2-chlorophenyl]sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CN(C(C)(C)C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)C(Cl)=C1 CIAFWUFOTHQPJN-VPUSJEBWSA-N 0.000 description 2
- XZIBMMVHGHMBAD-CFILVAQYSA-N (2s,4r)-4-[4-(benzimidazol-1-yl)-2-(trifluoromethyl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1C2=CC=CC=C2N=C1)NC1(C#N)CC1 XZIBMMVHGHMBAD-CFILVAQYSA-N 0.000 description 2
- SIXGHPIVIMLXEO-IYJPBCIQSA-N (2s,4r)-4-[4-bromo-2-(trifluoromethyl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC(Br)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 SIXGHPIVIMLXEO-IYJPBCIQSA-N 0.000 description 2
- AMDJQZVBNMRALE-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 AMDJQZVBNMRALE-ZBFHGGJFSA-N 0.000 description 2
- ADTNMIPKLMILBV-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-methoxyethyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CCOC)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 ADTNMIPKLMILBV-HIFRSBDPSA-N 0.000 description 2
- ZODMAVJYSJCFIH-KDOFPFPSSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2-nitrophenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound [O-][N+](=O)C1=CC=CC=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 ZODMAVJYSJCFIH-KDOFPFPSSA-N 0.000 description 2
- KGYZXGKIAHLLOT-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)N1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 KGYZXGKIAHLLOT-AEFFLSMTSA-N 0.000 description 2
- JTAQREJKZUVYMP-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2,2,2-trifluoroethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)CN1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 JTAQREJKZUVYMP-ZBFHGGJFSA-N 0.000 description 2
- VFEMSVWYPSRFIO-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-methylpropyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)CN1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 VFEMSVWYPSRFIO-MJGOQNOKSA-N 0.000 description 2
- GQDSIZYUUIQDAM-IRLDBZIGSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(3-methylphenyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(C)C=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 GQDSIZYUUIQDAM-IRLDBZIGSA-N 0.000 description 2
- NJFKAFAJMDEWQT-XQKZEKTMSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,3-dichlorophenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)=C1Cl NJFKAFAJMDEWQT-XQKZEKTMSA-N 0.000 description 2
- KPMBYVBJDKHUSN-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(3-methylbutanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC(C)C)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)NC1(C#N)CC1 KPMBYVBJDKHUSN-ZBFHGGJFSA-N 0.000 description 2
- JOCVWIZJUMIYEH-IYJPBCIQSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC(Cl)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 JOCVWIZJUMIYEH-IYJPBCIQSA-N 0.000 description 2
- DBAPCUKHQGDKSZ-IYJPBCIQSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-difluorophenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 DBAPCUKHQGDKSZ-IYJPBCIQSA-N 0.000 description 2
- JDOSVMFIODCRMA-DFQHDRSWSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dimethylphenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.CC1=CC(C)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 JDOSVMFIODCRMA-DFQHDRSWSA-N 0.000 description 2
- UPVPQHGIOHPWPL-KATIXKQHSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,6-dichlorophenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 UPVPQHGIOHPWPL-KATIXKQHSA-N 0.000 description 2
- AOYLWGDOGMIIOE-DFQHDRSWSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2-ethylphenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.CCC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 AOYLWGDOGMIIOE-DFQHDRSWSA-N 0.000 description 2
- SMMKARBXYPMNKP-RCPFAERMSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(4-imidazol-1-ylphenyl)sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C=1C=CC(=CC=1)N1C=NC=C1)NC1(C#N)CC1 SMMKARBXYPMNKP-RCPFAERMSA-N 0.000 description 2
- TVRSCJPQYFVMAO-KZCZEQIWSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(hydroxymethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.OCC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 TVRSCJPQYFVMAO-KZCZEQIWSA-N 0.000 description 2
- FEQAIESEIATEGS-DHXVBOOMSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethoxy)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.FC(F)(F)OC1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 FEQAIESEIATEGS-DHXVBOOMSA-N 0.000 description 2
- WZAOKIKCWYVWJM-PWSUYJOCSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]pyrrolidine-2-carboxamide Chemical compound S1C(C(F)(F)F)=NN=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 WZAOKIKCWYVWJM-PWSUYJOCSA-N 0.000 description 2
- BXJQRIRTPLLMQD-OCCSQVGLSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC(F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 BXJQRIRTPLLMQD-OCCSQVGLSA-N 0.000 description 2
- TVBURIMFZSJQOK-XMZRARIVSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-morpholin-4-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1CCOCC1)NC1(C#N)CC1 TVBURIMFZSJQOK-XMZRARIVSA-N 0.000 description 2
- MNKSAMHPACYNFS-DYVFJYSZSA-N (2s,4r)-n-(cyanomethyl)-1-(2-nitrophenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound [O-][N+](=O)C1=CC=CC=C1N1[C@H](C(=O)NCC#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 MNKSAMHPACYNFS-DYVFJYSZSA-N 0.000 description 2
- PJPMWHYDGWXPKG-WBVHZDCISA-N (2s,4r)-n-(cyanomethyl)-1-(4-fluorobenzoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=CC(F)=CC=C1C(=O)N1[C@H](C(=O)NCC#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 PJPMWHYDGWXPKG-WBVHZDCISA-N 0.000 description 2
- VPUSDGWLOZLERH-AEFFLSMTSA-N (2s,4r)-n-(cyanomethyl)-1-(4-methylbenzoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=CC(C)=CC=C1C(=O)N1[C@H](C(=O)NCC#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 VPUSDGWLOZLERH-AEFFLSMTSA-N 0.000 description 2
- WKHBBHACLDZOQD-WBVHZDCISA-N (2s,4r)-n-(cyanomethyl)-1-(cyclohexanecarbonyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2CCCCC2)[C@H](C(=O)NCC#N)C1 WKHBBHACLDZOQD-WBVHZDCISA-N 0.000 description 2
- UWZJSJOKBKHEBD-ZBFHGGJFSA-N (2s,4r)-n-(cyanomethyl)-1-(pyridine-4-carbonyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C=2C=CN=CC=2)[C@H](C(=O)NCC#N)C1 UWZJSJOKBKHEBD-ZBFHGGJFSA-N 0.000 description 2
- ZIXCKARMJWWYLM-AEFFLSMTSA-N (4-fluorophenyl) (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound C1=CC(F)=CC=C1OC(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)Cl)C1 ZIXCKARMJWWYLM-AEFFLSMTSA-N 0.000 description 2
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 2
- GILIYJDBJZWGBG-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-ol Chemical compound CC(O)C(F)(F)F GILIYJDBJZWGBG-UHFFFAOYSA-N 0.000 description 2
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
- LHQMNMRUORPCFV-UHFFFAOYSA-N 1-(2-bromoethylsulfanyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1SCCBr LHQMNMRUORPCFV-UHFFFAOYSA-N 0.000 description 2
- BVFAGBKXELCEPC-UHFFFAOYSA-N 1-(2-bromoethylsulfonyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)CCBr BVFAGBKXELCEPC-UHFFFAOYSA-N 0.000 description 2
- CXJIYLMHBPNFOQ-UHFFFAOYSA-N 1-(2-phenylphenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC=C1C1=CC=CC=C1 CXJIYLMHBPNFOQ-UHFFFAOYSA-N 0.000 description 2
- IKPLVIITWAFUPH-UHFFFAOYSA-N 1-(2-tert-butylphenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)C1=CC=CC=C1N1C(C(O)=O)CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 IKPLVIITWAFUPH-UHFFFAOYSA-N 0.000 description 2
- PFYOBZNMCYQFTO-UHFFFAOYSA-N 1-(3-cyanophenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC(C#N)=C1 PFYOBZNMCYQFTO-UHFFFAOYSA-N 0.000 description 2
- ZJNKQXKFPFVZIU-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(Cl)N=CC=1C1(C(=O)O)CC1 ZJNKQXKFPFVZIU-UHFFFAOYSA-N 0.000 description 2
- JYSJAUYGVPKULX-UHFFFAOYSA-N 1-(oxan-4-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1CCOCC1 JYSJAUYGVPKULX-UHFFFAOYSA-N 0.000 description 2
- OTEYEVBOYSZBOO-UHFFFAOYSA-N 1-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(C(O)=O)CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 OTEYEVBOYSZBOO-UHFFFAOYSA-N 0.000 description 2
- SUYGEVZWODUNRP-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC(C(F)(F)F)=C1 SUYGEVZWODUNRP-UHFFFAOYSA-N 0.000 description 2
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 2
- HCKNAJXCHMACDN-UHFFFAOYSA-N 1-methylpiperidine-4-carboxylic acid Chemical compound CN1CCC(C(O)=O)CC1 HCKNAJXCHMACDN-UHFFFAOYSA-N 0.000 description 2
- WUIJTQZXUURFQU-UHFFFAOYSA-N 1-methylsulfonylethene Chemical compound CS(=O)(=O)C=C WUIJTQZXUURFQU-UHFFFAOYSA-N 0.000 description 2
- ZNRDIZUBLMIBRP-UHFFFAOYSA-N 1-naphthalen-1-yl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1N(C=2C3=CC=CC=C3C=CC=2)C(C(=O)O)CC1S(=O)(=O)C1=CC=CC=C1C(F)(F)F ZNRDIZUBLMIBRP-UHFFFAOYSA-N 0.000 description 2
- YMEJMZDBUZSQEY-YPMHNXCESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(2-chlorophenyl)sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl YMEJMZDBUZSQEY-YPMHNXCESA-N 0.000 description 2
- GEXOQTQAUYONEJ-KGLIPLIRSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(benzenesulfonyl)pyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1 GEXOQTQAUYONEJ-KGLIPLIRSA-N 0.000 description 2
- MZMNEDXVUJLQAF-SFYZADRCSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C MZMNEDXVUJLQAF-SFYZADRCSA-N 0.000 description 2
- MZMNEDXVUJLQAF-YUMQZZPRSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@H](O)CN1C(=O)OC(C)(C)C MZMNEDXVUJLQAF-YUMQZZPRSA-N 0.000 description 2
- VNOMEAQPOMDWSR-UHFFFAOYSA-N 2,2,2-trifluoro-1-phenylethanol Chemical compound FC(F)(F)C(O)C1=CC=CC=C1 VNOMEAQPOMDWSR-UHFFFAOYSA-N 0.000 description 2
- OPMFFAOEPFATTG-UHFFFAOYSA-N 2,2,2-trifluoroethylhydrazine Chemical compound NNCC(F)(F)F OPMFFAOEPFATTG-UHFFFAOYSA-N 0.000 description 2
- QHZUUSNAUOEJBB-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropyl trifluoromethanesulfonate Chemical compound FC(F)(F)C(F)(F)COS(=O)(=O)C(F)(F)F QHZUUSNAUOEJBB-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- GWULLRAWYPECLK-UHFFFAOYSA-N 2-amino-2-phenylpropanenitrile;hydrochloride Chemical compound Cl.N#CC(N)(C)C1=CC=CC=C1 GWULLRAWYPECLK-UHFFFAOYSA-N 0.000 description 2
- RXATZPCCMYMPME-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1Cl RXATZPCCMYMPME-UHFFFAOYSA-N 0.000 description 2
- JXKUSPGMGMPURG-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)-1,3,4-thiadiazole Chemical compound FC(F)(F)C1=NN=C(Cl)S1 JXKUSPGMGMPURG-UHFFFAOYSA-N 0.000 description 2
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 2
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 2
- ASLZNAAQCGLWIV-UHFFFAOYSA-N 4-(2-chloro-4-fluorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)C1CN(C=2C(=CC=CN=2)C(F)(F)F)C(C(=O)NC2(CC2)C#N)C1 ASLZNAAQCGLWIV-UHFFFAOYSA-N 0.000 description 2
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
- XBPGBNVNPXUGPS-UHFFFAOYSA-N 4-bromo-2-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC(Br)=CC=C1S XBPGBNVNPXUGPS-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- ICQHVQJVRZINSO-UHFFFAOYSA-N 4-hydrazinyl-1h-pyridin-2-one Chemical compound NNC=1C=CNC(=O)C=1 ICQHVQJVRZINSO-UHFFFAOYSA-N 0.000 description 2
- OTLNPYWUJOZPPA-UHFFFAOYSA-M 4-nitrobenzoate Chemical compound [O-]C(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-M 0.000 description 2
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 208000004434 Calcinosis Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- DPPQTIRJIQBXAM-UHFFFAOYSA-N FC1=CC(=C(C=C1)S(=O)(=O)Cl)C(F)(F)F.FC1=CC(=C(C=C1)S)C(F)(F)F Chemical compound FC1=CC(=C(C=C1)S(=O)(=O)Cl)C(F)(F)F.FC1=CC(=C(C=C1)S)C(F)(F)F DPPQTIRJIQBXAM-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
- FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 2
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- RXBKMJIPNDOHFR-UHFFFAOYSA-N Phenelzine sulfate Chemical compound OS(O)(=O)=O.NNCCC1=CC=CC=C1 RXBKMJIPNDOHFR-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- OGSYCVCLXAFDNE-UHFFFAOYSA-N [cyano(phenyl)methyl]azanium;chloride Chemical compound [Cl-].N#CC([NH3+])C1=CC=CC=C1 OGSYCVCLXAFDNE-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001298 alcohols Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 150000001543 aryl boronic acids Chemical class 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
- HCZSTEFHYFPVNX-UHFFFAOYSA-N benzyl 2-(benzenesulfonyl)-6,6-difluoro-2,3,5,7-tetrahydro-1h-pyrrolizine-8-carboxylate Chemical compound C1C(F)(F)CN2CC(S(=O)(=O)C=3C=CC=CC=3)CC21C(=O)OCC1=CC=CC=C1 HCZSTEFHYFPVNX-UHFFFAOYSA-N 0.000 description 2
- MSJHOJKVMMEMNX-UHFFFAOYSA-N benzylhydrazine;hydron;dichloride Chemical compound Cl.Cl.NNCC1=CC=CC=C1 MSJHOJKVMMEMNX-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 230000002308 calcification Effects 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940125961 compound 24 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
- JZRHODNPRNTXKO-UHFFFAOYSA-N cyclohexylhydrazine;hydrochloride Chemical compound Cl.NNC1CCCCC1 JZRHODNPRNTXKO-UHFFFAOYSA-N 0.000 description 2
- SMPNIVZHQPXOQH-WBVHZDCISA-N cyclopentyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC2CCCC2)[C@H](C(=O)NC2(CC2)C#N)C1 SMPNIVZHQPXOQH-WBVHZDCISA-N 0.000 description 2
- ZFQCRLNKHHXELH-UHFFFAOYSA-N cyclopentyl carbonochloridate Chemical compound ClC(=O)OC1CCCC1 ZFQCRLNKHHXELH-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 2
- UJTPZISIAWDGFF-UHFFFAOYSA-N ethenylsulfonylbenzene Chemical compound C=CS(=O)(=O)C1=CC=CC=C1 UJTPZISIAWDGFF-UHFFFAOYSA-N 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- CLSFABFUSSFLLP-IUODEOHRSA-N ethyl (2r,4r)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OCC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=NC=CC=C1C(F)(F)F CLSFABFUSSFLLP-IUODEOHRSA-N 0.000 description 2
- RZOFIYQXSIJSMG-UHFFFAOYSA-N ethyl 1-(2-phenylphenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC=C1C1=CC=CC=C1 RZOFIYQXSIJSMG-UHFFFAOYSA-N 0.000 description 2
- FHCSFQXAPSXOPN-UHFFFAOYSA-N ethyl 1-(2-tert-butylphenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC=C1C(C)(C)C FHCSFQXAPSXOPN-UHFFFAOYSA-N 0.000 description 2
- YYWNIUZXZNMCAT-UHFFFAOYSA-N ethyl 1-(3-cyanophenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC(C#N)=C1 YYWNIUZXZNMCAT-UHFFFAOYSA-N 0.000 description 2
- XXFAXIYJEIDUCC-UHFFFAOYSA-N ethyl 1-(oxan-4-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1CCOCC1 XXFAXIYJEIDUCC-UHFFFAOYSA-N 0.000 description 2
- WBKLJRXMBXSJBR-UHFFFAOYSA-N ethyl 1-[3-(trifluoromethyl)phenyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound CCOC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1=CC=CC(C(F)(F)F)=C1 WBKLJRXMBXSJBR-UHFFFAOYSA-N 0.000 description 2
- WLMWXUFBXXNTMD-UHFFFAOYSA-N ethyl 1-naphthalen-1-yl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C=2C3=CC=CC=C3C=CC=2)C(C(=O)OCC)CC1S(=O)(=O)C1=CC=CC=C1C(F)(F)F WLMWXUFBXXNTMD-UHFFFAOYSA-N 0.000 description 2
- LUXJLYYQNXXDLI-UHFFFAOYSA-N ethyl 2-(2-phenylanilino)acetate Chemical compound CCOC(=O)CNC1=CC=CC=C1C1=CC=CC=C1 LUXJLYYQNXXDLI-UHFFFAOYSA-N 0.000 description 2
- YVCLTTINPMKQGL-UHFFFAOYSA-N ethyl 2-(2-tert-butylanilino)acetate Chemical compound CCOC(=O)CNC1=CC=CC=C1C(C)(C)C YVCLTTINPMKQGL-UHFFFAOYSA-N 0.000 description 2
- QHVWNEPCWNCEJF-UHFFFAOYSA-N ethyl 2-(3-cyanoanilino)acetate Chemical compound CCOC(=O)CNC1=CC=CC(C#N)=C1 QHVWNEPCWNCEJF-UHFFFAOYSA-N 0.000 description 2
- IIKWHPQJQHIWPR-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)-1,3-dioxolane-2-carboxylate Chemical compound C=1C=C(Br)C=CC=1C1(C(=O)OCC)OCCO1 IIKWHPQJQHIWPR-UHFFFAOYSA-N 0.000 description 2
- GYKRDEBTTIDYEQ-UHFFFAOYSA-N ethyl 2-(naphthalen-1-ylamino)acetate Chemical compound C1=CC=C2C(NCC(=O)OCC)=CC=CC2=C1 GYKRDEBTTIDYEQ-UHFFFAOYSA-N 0.000 description 2
- PPVCWFFTBXMYSQ-UHFFFAOYSA-N ethyl 2-(oxan-4-ylamino)acetate Chemical compound CCOC(=O)CNC1CCOCC1 PPVCWFFTBXMYSQ-UHFFFAOYSA-N 0.000 description 2
- SXAIOMBBQSGXRC-UHFFFAOYSA-N ethyl 2-[3-(trifluoromethyl)anilino]acetate Chemical compound CCOC(=O)CNC1=CC=CC(C(F)(F)F)=C1 SXAIOMBBQSGXRC-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 125000005348 fluorocycloalkyl group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- GMXFZBZOVZOYNQ-UHFFFAOYSA-N hydron;(3-methoxyphenyl)hydrazine;chloride Chemical compound Cl.COC1=CC=CC(NN)=C1 GMXFZBZOVZOYNQ-UHFFFAOYSA-N 0.000 description 2
- SHTBTGXNVWYODU-UHFFFAOYSA-N hydron;(3-methylphenyl)hydrazine;chloride Chemical compound Cl.CC1=CC=CC(NN)=C1 SHTBTGXNVWYODU-UHFFFAOYSA-N 0.000 description 2
- WRAUKLFJWHVIGP-UHFFFAOYSA-N hydron;quinolin-4-ylhydrazine;chloride Chemical compound Cl.C1=CC=C2C(NN)=CC=NC2=C1 WRAUKLFJWHVIGP-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 125000004401 m-toluyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C(*)=O 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- RHKNBBSYKNFQPU-UYAOXDASSA-N methyl (2r,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1CC1=CC=CC=C1 RHKNBBSYKNFQPU-UYAOXDASSA-N 0.000 description 2
- VNWVEBOZYMSHIU-NVXWUHKLSA-N methyl (2r,4r)-1-(2-cyclobutyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1CCC1 VNWVEBOZYMSHIU-NVXWUHKLSA-N 0.000 description 2
- SXQJWTCAZNSFEH-IEBWSBKVSA-N methyl (2r,4r)-1-(2-cyclohexyl-5-methylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1CCCCC1 SXQJWTCAZNSFEH-IEBWSBKVSA-N 0.000 description 2
- NVRHASDUMMKECW-TZIWHRDSSA-N methyl (2r,4r)-1-[2-(3-acetamidophenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1=CC=CC(NC(C)=O)=C1 NVRHASDUMMKECW-TZIWHRDSSA-N 0.000 description 2
- FZERGZLKRIROLR-UYAOXDASSA-N methyl (2r,4r)-1-[2-(3-methoxyphenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1=CC=CC(OC)=C1 FZERGZLKRIROLR-UYAOXDASSA-N 0.000 description 2
- JAFXEESPGZPMIN-NVXWUHKLSA-N methyl (2r,4r)-1-[5-methyl-2-(2-methylpropyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1CC(C)C JAFXEESPGZPMIN-NVXWUHKLSA-N 0.000 description 2
- FOTHFFNYRULJLB-TZIWHRDSSA-N methyl (2r,4r)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1CCC1=CC=CC=C1 FOTHFFNYRULJLB-TZIWHRDSSA-N 0.000 description 2
- BUCDGDQPMBNHIR-YPMHNXCESA-N methyl (2s,4r)-1-(3-oxobutanethioyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C(=S)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F BUCDGDQPMBNHIR-YPMHNXCESA-N 0.000 description 2
- YGCVOLYOISJGAI-OCCSQVGLSA-N methyl (2s,4r)-1-(3-oxobutanoyl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C(=O)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(OCC(F)(F)F)C=C1C(F)(F)F YGCVOLYOISJGAI-OCCSQVGLSA-N 0.000 description 2
- IKKUPKMGQNWRRV-WBVHZDCISA-N methyl (2s,4r)-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C(C)C IKKUPKMGQNWRRV-WBVHZDCISA-N 0.000 description 2
- XVXFNBQCYREMDA-SCZZXKLOSA-N methyl (2s,4r)-4-(2-chlorophenyl)sulfonylpyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl XVXFNBQCYREMDA-SCZZXKLOSA-N 0.000 description 2
- UGHHXFREZYPRSN-UXHICEINSA-N methyl (2s,4r)-4-(benzenesulfonyl)-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C=CC=CC=2)N1C1=CC(C)=NN1C1=CC=C(C(F)(F)F)C=C1 UGHHXFREZYPRSN-UXHICEINSA-N 0.000 description 2
- ZYUBYEUXMHOIFF-SCZZXKLOSA-N methyl (2s,4r)-4-[4-bromo-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(Br)C=C1C(F)(F)F ZYUBYEUXMHOIFF-SCZZXKLOSA-N 0.000 description 2
- DZZPCIUOLLMCIC-SCZZXKLOSA-N methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(F)C=C1C(F)(F)F DZZPCIUOLLMCIC-SCZZXKLOSA-N 0.000 description 2
- CVXXHXPNTZBZEL-UHFFFAOYSA-N methyl 4-carbonochloridoylbenzoate Chemical compound COC(=O)C1=CC=C(C(Cl)=O)C=C1 CVXXHXPNTZBZEL-UHFFFAOYSA-N 0.000 description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- HPPKRBHUNRRQLS-UHFFFAOYSA-N n-(3-hydrazinylphenyl)acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=CC(NN)=C1 HPPKRBHUNRRQLS-UHFFFAOYSA-N 0.000 description 2
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 2
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- CYCWBZMKKCTOGR-UHFFFAOYSA-N oxan-4-ylhydrazine;hydrochloride Chemical compound Cl.NNC1CCOCC1 CYCWBZMKKCTOGR-UHFFFAOYSA-N 0.000 description 2
- AVPKHOTUOHDTLW-UHFFFAOYSA-N oxane-4-carboxylic acid Chemical compound OC(=O)C1CCOCC1 AVPKHOTUOHDTLW-UHFFFAOYSA-N 0.000 description 2
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 2
- 125000005440 p-toluyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C(*)=O)C([H])([H])[H] 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- YTRGNBTVTHPFJM-UHFFFAOYSA-N pyridazin-3-ylhydrazine Chemical compound NNC1=CC=CN=N1 YTRGNBTVTHPFJM-UHFFFAOYSA-N 0.000 description 2
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- XZPHHHOUBHWESE-DOMZBBRYSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,6-dichlorophenyl)sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1Cl)Cl)NC1(C#N)CC1 XZPHHHOUBHWESE-DOMZBBRYSA-N 0.000 description 2
- PKRYLALGJVVTEX-KGLIPLIRSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2-methylpropylsulfonyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@H](S(=O)(=O)CC(C)C)C[C@H]1C(=O)NC1(C#N)CC1 PKRYLALGJVVTEX-KGLIPLIRSA-N 0.000 description 2
- OQYUTLXOOVHGOU-AEFFLSMTSA-N tert-butyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclohexyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CCCCC1 OQYUTLXOOVHGOU-AEFFLSMTSA-N 0.000 description 2
- AQGMGNKCSJEICY-CABCVRRESA-N tert-butyl (2s,4r)-4-[4-chloro-2-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(Cl)=CC=1)OCC(F)(F)F)NC1(C#N)CC1 AQGMGNKCSJEICY-CABCVRRESA-N 0.000 description 2
- CXPRGLWJJQBWRS-UHFFFAOYSA-N tert-butyl 3-cyclopropyl-3-oxopropanoate Chemical compound CC(C)(C)OC(=O)CC(=O)C1CC1 CXPRGLWJJQBWRS-UHFFFAOYSA-N 0.000 description 2
- BWSVCIPDXWEGMQ-UHFFFAOYSA-N tert-butyl 4-[(2-ethoxy-2-oxoethyl)amino]piperidine-1-carboxylate Chemical compound CCOC(=O)CNC1CCN(C(=O)OC(C)(C)C)CC1 BWSVCIPDXWEGMQ-UHFFFAOYSA-N 0.000 description 2
- IHMQNZFRFVYNDS-UHFFFAOYSA-N tert-butyl n-amino-n-methylcarbamate Chemical compound CN(N)C(=O)OC(C)(C)C IHMQNZFRFVYNDS-UHFFFAOYSA-N 0.000 description 2
- DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- WAWSGFGXFSUXIA-IMJSIDKUSA-N (1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one Chemical compound C1N[C@]2([H])C(=O)O[C@@]1([H])C2 WAWSGFGXFSUXIA-IMJSIDKUSA-N 0.000 description 1
- FDLDBBWXFXMLIT-UHFFFAOYSA-N (2,6-dimethylpyridin-4-yl)hydrazine;hydrochloride Chemical compound Cl.CC1=CC(NN)=CC(C)=N1 FDLDBBWXFXMLIT-UHFFFAOYSA-N 0.000 description 1
- KLJQMDAUTPVNCU-UHFFFAOYSA-N (2-methyl-1h-pyridin-2-yl)hydrazine Chemical compound NNC1(C)NC=CC=C1 KLJQMDAUTPVNCU-UHFFFAOYSA-N 0.000 description 1
- FYWFCRHZXORPFH-UHFFFAOYSA-N (2-sulfanylphenyl)methanol Chemical compound OCC1=CC=CC=C1S FYWFCRHZXORPFH-UHFFFAOYSA-N 0.000 description 1
- XQTWJBCNGSDXDM-WHCXFUJUSA-N (2R)-1-[1-(6-chloropyridin-3-yl)cyclopropanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)[C@@H]1N(CC(C1)S(=O)(=O)C1=C(C=C(C=C1)OCC(F)(F)F)Cl)C(=O)C1(CC1)C=1C=NC(=CC1)Cl XQTWJBCNGSDXDM-WHCXFUJUSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- FLPSCHWUPGJNRH-GLGOKHISSA-N (2R)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C(#N)C1(CC1)NC(=O)[C@@H]1NCC(C1)S(=O)(=O)C1=C(C=C(C=C1)OCC(F)(F)F)Cl FLPSCHWUPGJNRH-GLGOKHISSA-N 0.000 description 1
- AHBMQVMGIFFPFM-CSODHUTKSA-N (2R,4S,5R)-2-[(1-cyanocyclopropyl)carbamoyl]-5-(4-fluorophenyl)-2-(2-methylpropyl)-4-methylsulfonylpyrrolidine-1-carboxylic acid Chemical compound C1([C@@H]2[C@H](C[C@](N2C(O)=O)(CC(C)C)C(=O)NC2(CC2)C#N)S(C)(=O)=O)=CC=C(F)C=C1 AHBMQVMGIFFPFM-CSODHUTKSA-N 0.000 description 1
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
- KNTAGJAUNUADAA-KOLCDFICSA-N (2S,4R)-2-(cyanomethylcarbamoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylic acid Chemical compound C1[C@@H](C(=O)NCC#N)N(C(=O)O)C[C@@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F KNTAGJAUNUADAA-KOLCDFICSA-N 0.000 description 1
- LLVLVPBVFLNNAF-KOLCDFICSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,3-dichlorophenyl)sulfonylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=C(Cl)C=CC=1)Cl)NC1(C#N)CC1 LLVLVPBVFLNNAF-KOLCDFICSA-N 0.000 description 1
- FZNFVXVKSOOQRB-PWSUYJOCSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,4-difluorophenyl)sulfanylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)SC=1C(=CC(F)=CC=1)F)NC1(C#N)CC1 FZNFVXVKSOOQRB-PWSUYJOCSA-N 0.000 description 1
- PUGZKQFVMDBCAU-KGLIPLIRSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,4-dimethylphenyl)sulfonylpyrrolidine-1-carboxylic acid Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)[C@H]1CN(C(O)=O)[C@H](C(=O)NC2(CC2)C#N)C1 PUGZKQFVMDBCAU-KGLIPLIRSA-N 0.000 description 1
- DNTJZJSPGABXIS-SKDRFNHKSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,6-dichlorophenyl)sulfanylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)SC=1C(=CC=CC=1Cl)Cl)NC1(C#N)CC1 DNTJZJSPGABXIS-SKDRFNHKSA-N 0.000 description 1
- MGBUECGXUBWPNC-CVEARBPZSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(4-imidazol-1-ylphenyl)sulfonylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C=CC(=CC=1)N1C=NC=C1)NC1(C#N)CC1 MGBUECGXUBWPNC-CVEARBPZSA-N 0.000 description 1
- SFVPFBLACUHRFJ-OLZOCXBDSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[2-(hydroxymethyl)phenyl]sulfonylpyrrolidine-1-carboxylic acid Chemical compound OCC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(O)=O)[C@H](C(=O)NC2(CC2)C#N)C1 SFVPFBLACUHRFJ-OLZOCXBDSA-N 0.000 description 1
- MNVMMIBVNGRTJP-HIFRSBDPSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[4-pyrazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)C(F)(F)F)NC1(C#N)CC1 MNVMMIBVNGRTJP-HIFRSBDPSA-N 0.000 description 1
- DKIKIKLVAWOVDR-RQJHMYQMSA-N (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-hydroxypyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1C[C@H](O)C[C@H]1C(=O)NC1(C#N)CC1 DKIKIKLVAWOVDR-RQJHMYQMSA-N 0.000 description 1
- CDYBKXYVAUCQFN-VFXSIBAZSA-N (2S,4R)-2-[[cyano(cyclopropyl)methyl]carbamoyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC(C#N)C1CC1 CDYBKXYVAUCQFN-VFXSIBAZSA-N 0.000 description 1
- BFAKTTSVHVCTIB-PWSUYJOCSA-N (2S,4R)-4-(2-chloro-4-fluorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(F)=CC=1)Cl)NC1(C#N)CC1 BFAKTTSVHVCTIB-PWSUYJOCSA-N 0.000 description 1
- ULOQGWXPOTUEHZ-PWSUYJOCSA-N (2S,4R)-4-(2-chlorophenyl)sulfonyl-2-(2-cyanopropan-2-ylcarbamoyl)pyrrolidine-1-carboxylic acid Chemical compound C1N(C(O)=O)[C@H](C(=O)NC(C)(C)C#N)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl ULOQGWXPOTUEHZ-PWSUYJOCSA-N 0.000 description 1
- SPZCSDPNKWIECT-KOLCDFICSA-N (2S,4R)-4-(2-chlorophenyl)sulfonyl-2-(cyanomethylcarbamoyl)pyrrolidine-1-carboxylic acid Chemical compound C1[C@@H](C(=O)NCC#N)N(C(=O)O)C[C@@H]1S(=O)(=O)C1=CC=CC=C1Cl SPZCSDPNKWIECT-KOLCDFICSA-N 0.000 description 1
- HZAZWHTUYUMZFO-YPMHNXCESA-N (2S,4R)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclobutyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CCC1 HZAZWHTUYUMZFO-YPMHNXCESA-N 0.000 description 1
- XKOXRZCOFFFTCU-HIFRSBDPSA-N (2S,4R)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclohexyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CCCCC1 XKOXRZCOFFFTCU-HIFRSBDPSA-N 0.000 description 1
- VWLFHDJYQXDEPB-AQYZNVCMSA-N (2S,4R)-4-(2-chlorophenyl)sulfonyl-2-[[cyano(phenyl)methyl]carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC(C#N)C1=CC=CC=C1 VWLFHDJYQXDEPB-AQYZNVCMSA-N 0.000 description 1
- ZAJOAFYLNZYEQX-OLZOCXBDSA-N (2S,4R)-4-(4-chloro-2-methylphenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound CC1=CC(Cl)=CC=C1S(=O)(=O)[C@H]1CN(C(O)=O)[C@H](C(=O)NC2(CC2)C#N)C1 ZAJOAFYLNZYEQX-OLZOCXBDSA-N 0.000 description 1
- XKZATVJORGWXNN-VOHIISRTSA-N (2S,4R)-4-[2-chloro-4-(1,1,1-trifluoropropan-2-yloxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound ClC1=CC(OC(C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(O)=O)[C@H](C(=O)NC2(CC2)C#N)C1 XKZATVJORGWXNN-VOHIISRTSA-N 0.000 description 1
- JZKDCCWKONSNQT-ZBFHGGJFSA-N (2S,4R)-4-[2-chloro-4-(4,4-difluoropiperidin-1-yl)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1CCC(F)(F)CC1)Cl)NC1(C#N)CC1 JZKDCCWKONSNQT-ZBFHGGJFSA-N 0.000 description 1
- LSYVIZSSQWEFPD-AEFFLSMTSA-N (2S,4R)-4-[2-chloro-4-(4-ethylpiperazin-1-yl)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound C1CN(CC)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(O)=O)C(Cl)=C1 LSYVIZSSQWEFPD-AEFFLSMTSA-N 0.000 description 1
- ZHSKVKONBSYACT-HIFRSBDPSA-N (2S,4R)-4-[2-chloro-4-(oxetan-3-yloxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(OC2COC2)=CC=1)Cl)NC1(C#N)CC1 ZHSKVKONBSYACT-HIFRSBDPSA-N 0.000 description 1
- AQYXZOQFSUVGKD-PWSUYJOCSA-N (2S,4R)-4-[4-bromo-2-(trifluoromethyl)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(Br)=CC=1)C(F)(F)F)NC1(C#N)CC1 AQYXZOQFSUVGKD-PWSUYJOCSA-N 0.000 description 1
- GILIYJDBJZWGBG-REOHCLBHSA-N (2s)-1,1,1-trifluoropropan-2-ol Chemical compound C[C@H](O)C(F)(F)F GILIYJDBJZWGBG-REOHCLBHSA-N 0.000 description 1
- ZFBIWMSGOQQHAF-YPMHNXCESA-N (2s,4r)-1-(1,5-dimethylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CN1C(C)=CC(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(O)=O)=N1 ZFBIWMSGOQQHAF-YPMHNXCESA-N 0.000 description 1
- QIWMJYFEGHOSGE-YPMHNXCESA-N (2s,4r)-1-(2,5-dimethylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CN1N=C(C)C=C1N1[C@H](C(O)=O)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 QIWMJYFEGHOSGE-YPMHNXCESA-N 0.000 description 1
- LLPJVYSSWITXEF-IRLDBZIGSA-N (2s,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1CC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 LLPJVYSSWITXEF-IRLDBZIGSA-N 0.000 description 1
- UVLVAEIAEXXBGU-MSOLQXFVSA-N (2s,4r)-1-(2-benzyl-5-methylpyrazol-3-yl)-4-(cyclopropylmethylsulfonyl)pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1CC=1C=CC=CC=1)C)(=O)CC1CC1 UVLVAEIAEXXBGU-MSOLQXFVSA-N 0.000 description 1
- FVFFSVIJMULRFV-ABAIWWIYSA-N (2s,4r)-1-(2-nitrophenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C[C@H]1C(=O)O)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC=CC=C1[N+]([O-])=O FVFFSVIJMULRFV-ABAIWWIYSA-N 0.000 description 1
- SIAOXUDVVICUEX-PWSUYJOCSA-N (2s,4r)-1-(3-chloro-1,2,4-thiadiazol-5-yl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C=2SN=C(Cl)N=2)[C@H](C(=O)NC2(CC2)C#N)C1 SIAOXUDVVICUEX-PWSUYJOCSA-N 0.000 description 1
- XTOCKLMEWOHIFG-KDOFPFPSSA-N (2s,4r)-1-(3-chloro-4-fluorophenyl)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=C(Cl)C(F)=CC=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 XTOCKLMEWOHIFG-KDOFPFPSSA-N 0.000 description 1
- PQXGCNYJSMLNPD-PWSUYJOCSA-N (2s,4r)-1-(5-methyl-1h-pyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound N1C(C)=CC(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(O)=O)=N1 PQXGCNYJSMLNPD-PWSUYJOCSA-N 0.000 description 1
- LSWOGNBOQFPMRK-AEFFLSMTSA-N (2s,4r)-1-(5-methyl-2-phenylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=CC=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F LSWOGNBOQFPMRK-AEFFLSMTSA-N 0.000 description 1
- ZENNKANXKLZMDX-HIFRSBDPSA-N (2s,4r)-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound CC(C)N1N=C(C)C=C1N1[C@H](C(O)=O)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 ZENNKANXKLZMDX-HIFRSBDPSA-N 0.000 description 1
- AIBSDLHFAFCXAJ-HIFRSBDPSA-N (2s,4r)-1-(5-methyl-2-pyridazin-3-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1N=NC=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F AIBSDLHFAFCXAJ-HIFRSBDPSA-N 0.000 description 1
- JYSMYUOYMZQKCV-IERDGZPVSA-N (2s,4r)-1-(5-methyl-2-quinolin-4-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C2=CC=CC=C2N=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F JYSMYUOYMZQKCV-IERDGZPVSA-N 0.000 description 1
- KXZCNUQSNGPPAE-AEFFLSMTSA-N (2s,4r)-1-(5-tert-butyl-2-methylpyrazole-3-carbonyl)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound CN1N=C(C(C)(C)C)C=C1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C1 KXZCNUQSNGPPAE-AEFFLSMTSA-N 0.000 description 1
- TVUHGOKNSKHDOB-PWSUYJOCSA-N (2s,4r)-1-[(2-methylpropan-2-yl)oxycarbonyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F TVUHGOKNSKHDOB-PWSUYJOCSA-N 0.000 description 1
- VFOFRWJAZZZNBG-CTNGQTDRSA-N (2s,4r)-1-[1-(3-bromophenyl)cyclopropanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=C(Br)C=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 VFOFRWJAZZZNBG-CTNGQTDRSA-N 0.000 description 1
- FFCUPZOPMAYQFV-CTNGQTDRSA-N (2s,4r)-1-[1-(3-chlorophenyl)cyclopropanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=C(Cl)C=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 FFCUPZOPMAYQFV-CTNGQTDRSA-N 0.000 description 1
- QSXYSASUDCLWJZ-QUCCMNQESA-N (2s,4r)-1-[1-(4-bromophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Br)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 QSXYSASUDCLWJZ-QUCCMNQESA-N 0.000 description 1
- QLXZTOXWNPUFTK-CTNGQTDRSA-N (2s,4r)-1-[1-(4-bromophenyl)cyclopropanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Br)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 QLXZTOXWNPUFTK-CTNGQTDRSA-N 0.000 description 1
- JUCYOTGQFDBMGU-CTNGQTDRSA-N (2s,4r)-1-[1-(4-carbamoylphenyl)cyclopropanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(C(=O)N)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 JUCYOTGQFDBMGU-CTNGQTDRSA-N 0.000 description 1
- DKEKZSWWOYDFHZ-QUCCMNQESA-N (2s,4r)-1-[1-(4-chlorophenoxy)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1OC1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 DKEKZSWWOYDFHZ-QUCCMNQESA-N 0.000 description 1
- JXKGDDXJKJWWRW-CTNGQTDRSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclobutanecarbonyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)Cl)C(=O)NC2(CC2)C#N)CCC1 JXKGDDXJKJWWRW-CTNGQTDRSA-N 0.000 description 1
- SHDWIQRRPCVYEY-IRLDBZIGSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclobutanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CCC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 SHDWIQRRPCVYEY-IRLDBZIGSA-N 0.000 description 1
- CQECJHFXTVOTNU-VWNXMTODSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclohexanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CCCCC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 CQECJHFXTVOTNU-VWNXMTODSA-N 0.000 description 1
- ZPLMGLBGXRRJRM-GGAORHGYSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(=CC=2)N2N=CC=C2)Cl)C(=O)NC2(CC2)C#N)CC1 ZPLMGLBGXRRJRM-GGAORHGYSA-N 0.000 description 1
- PEFXHWPKZZFRAK-QUCCMNQESA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 PEFXHWPKZZFRAK-QUCCMNQESA-N 0.000 description 1
- VWYMCRTZLQZLBE-CTNGQTDRSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 VWYMCRTZLQZLBE-CTNGQTDRSA-N 0.000 description 1
- MDSKUHAUCCEMTL-NOZRDPDXSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-4-[2-chloro-4-(2-propan-2-ylimidazol-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound CC(C)C1=NC=CN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)C(Cl)=C1 MDSKUHAUCCEMTL-NOZRDPDXSA-N 0.000 description 1
- OEEWQYXUWJLSGT-QUCCMNQESA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 OEEWQYXUWJLSGT-QUCCMNQESA-N 0.000 description 1
- VMEYIAKIHZVSHY-QUCCMNQESA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)-4-(2,4-difluorophenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 VMEYIAKIHZVSHY-QUCCMNQESA-N 0.000 description 1
- FZTMJHOARIKTIJ-MOPGFXCFSA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)-4-(2-methylpropylsulfonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)CC(C)C)C(=O)NC1(CC1)C#N)C(=O)C1(C=2C=CC(Cl)=CC=2)CC1 FZTMJHOARIKTIJ-MOPGFXCFSA-N 0.000 description 1
- HQCCHMQLMMBRED-QUCCMNQESA-N (2s,4r)-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 HQCCHMQLMMBRED-QUCCMNQESA-N 0.000 description 1
- QPGFHXQIMYOMFG-AEFFLSMTSA-N (2s,4r)-1-[1-(6-chloropyridin-3-yl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=NC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 QPGFHXQIMYOMFG-AEFFLSMTSA-N 0.000 description 1
- RKBPBMWJPFVGPJ-NOZRDPDXSA-N (2s,4r)-1-[2,2-bis(4-chlorophenyl)acetyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 RKBPBMWJPFVGPJ-NOZRDPDXSA-N 0.000 description 1
- LHVZZGPYSGJQOU-MSOLQXFVSA-N (2s,4r)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-(cyclopropylmethylsulfonyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)S(=O)(=O)CC1CC1)NC1(C#N)CC1 LHVZZGPYSGJQOU-MSOLQXFVSA-N 0.000 description 1
- XAFWMVONBNQBRL-MJGOQNOKSA-N (2s,4r)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 XAFWMVONBNQBRL-MJGOQNOKSA-N 0.000 description 1
- YXRAPDCIMAWTLG-MJGOQNOKSA-N (2s,4r)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)S(=O)(=O)C=1C(=CC(F)=CC=1)C(F)(F)F)NC1(C#N)CC1 YXRAPDCIMAWTLG-MJGOQNOKSA-N 0.000 description 1
- ASJJUKAMOSBGKI-GGAORHGYSA-N (2s,4r)-1-[2-(3-acetamidophenyl)-5-methylpyrazol-3-yl]-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(=O)NC1=CC=CC(N2C(=CC(C)=N2)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=C1 ASJJUKAMOSBGKI-GGAORHGYSA-N 0.000 description 1
- KCJMNADVWFDXFC-CCJHYTBNSA-N (2s,4r)-1-[2-(4-aminocyclohexyl)acetyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CC(N)CCC1CC(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C1 KCJMNADVWFDXFC-CCJHYTBNSA-N 0.000 description 1
- FYXAVGJZEKOJMQ-QUCCMNQESA-N (2s,4r)-1-[2-(4-chlorophenyl)-2-methylpropanoyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C=1C=CC(Cl)=CC=1)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 FYXAVGJZEKOJMQ-QUCCMNQESA-N 0.000 description 1
- FMSWBRSTQCDWGJ-CTNGQTDRSA-N (2s,4r)-1-[2-(4-chlorophenyl)-2-methylpropanoyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C=1C=CC(Cl)=CC=1)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)NC1(C#N)CC1 FMSWBRSTQCDWGJ-CTNGQTDRSA-N 0.000 description 1
- ZXBVNQQQGZAZMD-QUCCMNQESA-N (2s,4r)-1-[2-(4-chlorophenyl)acetyl]-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)CC=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 ZXBVNQQQGZAZMD-QUCCMNQESA-N 0.000 description 1
- JEGNOLZJOVGVFW-JFSACEIJSA-N (2s,4r)-1-[2-(4-chlorophenyl)propanoyl]-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)C=1C=CC(Cl)=CC=1)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 JEGNOLZJOVGVFW-JFSACEIJSA-N 0.000 description 1
- CAXAGAVPVVBVFA-YPMHNXCESA-N (2s,4r)-1-[5-methyl-2-(2,2,2-trifluoroethyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound FC(F)(F)CN1N=C(C)C=C1N1[C@H](C(O)=O)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 CAXAGAVPVVBVFA-YPMHNXCESA-N 0.000 description 1
- GAMISEFGIRLMOU-AEFFLSMTSA-N (2s,4r)-1-[5-methyl-2-(2-methylpyridin-4-yl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=C(C)N=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F GAMISEFGIRLMOU-AEFFLSMTSA-N 0.000 description 1
- UGCXCCNJWCDJQP-MJGOQNOKSA-N (2s,4r)-1-[5-methyl-2-(3-methylphenyl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=C(C)C=CC=1)C)(=O)C1=CC=CC=C1C(F)(F)F UGCXCCNJWCDJQP-MJGOQNOKSA-N 0.000 description 1
- OYNLITUOEFLANS-MJGOQNOKSA-N (2s,4r)-1-acetyl-4-(2-chloro-4-piperidin-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC(=CC=1)N1CCCCC1)Cl)NC1(C#N)CC1 OYNLITUOEFLANS-MJGOQNOKSA-N 0.000 description 1
- UQCPXBPWOQJWOR-TWONFVHBSA-N (2s,4r)-1-acetyl-4-[2-chloro-4-(1,1,1-trifluoropropan-2-yloxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OC(C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(C)=O)[C@H](C(=O)NC2(CC2)C#N)C1 UQCPXBPWOQJWOR-TWONFVHBSA-N 0.000 description 1
- RNPZYOHQVIGXRE-OCCSQVGLSA-N (2s,4r)-1-acetyl-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 RNPZYOHQVIGXRE-OCCSQVGLSA-N 0.000 description 1
- MVVWHFANGJCLOH-AEFFLSMTSA-N (2s,4r)-1-benzoyl-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 MVVWHFANGJCLOH-AEFFLSMTSA-N 0.000 description 1
- NDFCFOJQDCTYGU-WBVHZDCISA-N (2s,4r)-1-benzoyl-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C=2C=CC=CC=2)[C@H](C(=O)NCC#N)C1 NDFCFOJQDCTYGU-WBVHZDCISA-N 0.000 description 1
- QUJRHKAHTOZDQD-PWSUYJOCSA-N (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,4-difluorophenyl)sulfonylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(F)=CC=1)F)NC1(C#N)CC1 QUJRHKAHTOZDQD-PWSUYJOCSA-N 0.000 description 1
- FROPAFBHCTYNTE-SKDRFNHKSA-N (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,6-dichlorophenyl)sulfonylpyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1Cl)Cl)NC1(C#N)CC1 FROPAFBHCTYNTE-SKDRFNHKSA-N 0.000 description 1
- BLEDCJZTXPFDSY-KOLCDFICSA-N (2s,4r)-4-(2,3-dichlorophenyl)sulfonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@@H]1S(=O)(=O)C1=CC=CC(Cl)=C1Cl BLEDCJZTXPFDSY-KOLCDFICSA-N 0.000 description 1
- APWLDGORIOOAOH-KGLIPLIRSA-N (2s,4r)-4-(2,4-dimethylphenyl)sulfonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(O)=O)C1 APWLDGORIOOAOH-KGLIPLIRSA-N 0.000 description 1
- ZGOQKDPUNRQNDU-OCCSQVGLSA-N (2s,4r)-4-(2-chloro-4-fluorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 ZGOQKDPUNRQNDU-OCCSQVGLSA-N 0.000 description 1
- AIDUSEZPBLMBPZ-APPZFPTMSA-N (2s,4r)-4-(2-chloro-4-fluorophenyl)sulfonylpyrrolidine-1,2-dicarboxylic acid Chemical compound C1N(C(O)=O)[C@H](C(=O)O)C[C@H]1S(=O)(=O)C1=CC=C(F)C=C1Cl AIDUSEZPBLMBPZ-APPZFPTMSA-N 0.000 description 1
- UCRYLQYTPHMXEO-GJZUVCINSA-N (2s,4r)-4-(2-chloro-4-imidazo[4,5-c]pyridin-1-ylphenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(=CC=2)N2C3=CC=NC=C3N=C2)Cl)C(=O)NC2(CC2)C#N)CC1 UCRYLQYTPHMXEO-GJZUVCINSA-N 0.000 description 1
- YPQYNNRXRXSJIG-GJZUVCINSA-N (2s,4r)-4-(2-chloro-4-imidazo[4,5-c]pyridin-5-ylphenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(=CC=2)N2C=C3N=CN=C3C=C2)Cl)C(=O)NC2(CC2)C#N)CC1 YPQYNNRXRXSJIG-GJZUVCINSA-N 0.000 description 1
- GAVQYVMNZDKGAP-GGAORHGYSA-N (2s,4r)-4-(2-chloro-4-imidazol-1-ylphenyl)sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(=CC=2)N2C=NC=C2)Cl)C(=O)NC2(CC2)C#N)CC1 GAVQYVMNZDKGAP-GGAORHGYSA-N 0.000 description 1
- VLXRPCUOCQQURI-AEFFLSMTSA-N (2s,4r)-4-(2-chloro-4-morpholin-4-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CCOCC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 VLXRPCUOCQQURI-AEFFLSMTSA-N 0.000 description 1
- OFEUJVSPIGSEJR-AEFFLSMTSA-N (2s,4r)-4-(2-chloro-4-piperazin-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CCNCC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 OFEUJVSPIGSEJR-AEFFLSMTSA-N 0.000 description 1
- BCQGWSYZGWSYIR-OCCSQVGLSA-N (2s,4r)-4-(2-chloro-4-piperidin-1-ylphenyl)sulfonylpyrrolidine-1,2-dicarboxylic acid Chemical compound C1N(C(O)=O)[C@H](C(=O)O)C[C@H]1S(=O)(=O)C1=CC=C(N2CCCCC2)C=C1Cl BCQGWSYZGWSYIR-OCCSQVGLSA-N 0.000 description 1
- YYWDKVJFQXEBGW-HIFRSBDPSA-N (2s,4r)-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)Cl)NC1(C#N)CC1 YYWDKVJFQXEBGW-HIFRSBDPSA-N 0.000 description 1
- OLUABKSCNUOOAJ-WBVHZDCISA-N (2s,4r)-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1N=CC=C1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 OLUABKSCNUOOAJ-WBVHZDCISA-N 0.000 description 1
- KSHXVEIYCBBRHT-HIFRSBDPSA-N (2s,4r)-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1Cl)N1N=CC=C1)NC1(C#N)CC1 KSHXVEIYCBBRHT-HIFRSBDPSA-N 0.000 description 1
- RLXYOYBSFCUABF-ZBFHGGJFSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-(2-cyclobutyl-5-methylpyrazol-3-yl)pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C1CCC1)C)(=O)C1=CC=CC=C1Cl RLXYOYBSFCUABF-ZBFHGGJFSA-N 0.000 description 1
- FGGXDCZOVXJYQA-PWSUYJOCSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@@H]1S(=O)(=O)C1=CC=CC=C1Cl FGGXDCZOVXJYQA-PWSUYJOCSA-N 0.000 description 1
- PBFHARMSFSJZAS-ZBFHGGJFSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)(=O)C1=CC=CC=C1Cl PBFHARMSFSJZAS-ZBFHGGJFSA-N 0.000 description 1
- CAYQLBNKGWRBGR-QUCCMNQESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1CCC=1C=CC=CC=1)C)(=O)C1=CC=CC=C1Cl CAYQLBNKGWRBGR-QUCCMNQESA-N 0.000 description 1
- KCUJPJUCPYJHJO-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)(=O)C1=CC=CC=C1Cl KCUJPJUCPYJHJO-AEFFLSMTSA-N 0.000 description 1
- FJCFBKMAVXMAKP-PWSUYJOCSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 FJCFBKMAVXMAKP-PWSUYJOCSA-N 0.000 description 1
- CVZHJKXGULMPQK-MNQXGVLQSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyano-1-phenylethyl)pyrrolidine-2-carboxamide Chemical compound O=S([C@@H]1C[C@H](NC1)C(=O)NC(C)(C#N)C=1C=CC=CC=1)(=O)C1=CC=CC=C1Cl CVZHJKXGULMPQK-MNQXGVLQSA-N 0.000 description 1
- DKNIQSUOPZMEPU-JPDAQUKBSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyano-1-phenylethyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=S([C@@H]1C[C@H](NC1)C(=O)NC(C)(C#N)C=1C=CC=CC=1)(=O)C1=CC=CC=C1Cl DKNIQSUOPZMEPU-JPDAQUKBSA-N 0.000 description 1
- VRVHLVCMEUDWJI-HIFRSBDPSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 VRVHLVCMEUDWJI-HIFRSBDPSA-N 0.000 description 1
- LQHBPGSGPXIFLD-HIFRSBDPSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2-dimethylpropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 LQHBPGSGPXIFLD-HIFRSBDPSA-N 0.000 description 1
- WGHWMGWTRCNULF-HIFRSBDPSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2-methylpropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 WGHWMGWTRCNULF-HIFRSBDPSA-N 0.000 description 1
- YCYCSKMPTHEPPC-QUCCMNQESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(2-phenylethyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(CCC=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 YCYCSKMPTHEPPC-QUCCMNQESA-N 0.000 description 1
- RDSMSDWKWMGVRL-RLSDIYDTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(3,3,3-trifluoro-2-methylpropyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1CC(C)C(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 RDSMSDWKWMGVRL-RLSDIYDTSA-N 0.000 description 1
- BTVHMZRBKPEUNR-YPMHNXCESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 BTVHMZRBKPEUNR-YPMHNXCESA-N 0.000 description 1
- FHAQNVFCCDFSNB-ZBFHGGJFSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(3-methylbutanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CC1 FHAQNVFCCDFSNB-ZBFHGGJFSA-N 0.000 description 1
- INRFUUGBUQATEI-VWNXMTODSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(4-phenylphenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(S(=O)(=O)C=2C=CC(=CC=2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 INRFUUGBUQATEI-VWNXMTODSA-N 0.000 description 1
- WXMASBJALYNWOI-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(cyclohexanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2CCCCC2)[C@H](C(=O)NC2(CC2)C#N)C1 WXMASBJALYNWOI-AEFFLSMTSA-N 0.000 description 1
- RZKMUBROWAVLLN-AEFFLSMTSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-(pyridin-4-ylmethyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(CC=2C=CN=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 RZKMUBROWAVLLN-AEFFLSMTSA-N 0.000 description 1
- CRPVARGKSIGJJN-UZLBHIALSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(3,4-dichlorophenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 CRPVARGKSIGJJN-UZLBHIALSA-N 0.000 description 1
- LZMAJHHQCOIDMA-QUCCMNQESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(4-iodophenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(I)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 LZMAJHHQCOIDMA-QUCCMNQESA-N 0.000 description 1
- QYLJTZKARDJLHL-OCCSQVGLSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 QYLJTZKARDJLHL-OCCSQVGLSA-N 0.000 description 1
- ITXPATABLFJKJW-QUCCMNQESA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-[4-(1,3-oxazol-5-yl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(S(=O)(=O)C=2C=CC(=CC=2)C=2OC=NC=2)[C@H](C(=O)NC2(CC2)C#N)C1 ITXPATABLFJKJW-QUCCMNQESA-N 0.000 description 1
- FOTCKCCCMWUXMG-ZBFHGGJFSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-cyclobutylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(C2CCC2)[C@H](C(=O)NC2(CC2)C#N)C1 FOTCKCCCMWUXMG-ZBFHGGJFSA-N 0.000 description 1
- UCRKBUCWUKGLCR-IRLDBZIGSA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(1-cyanocyclopropyl)-1-naphthalen-2-ylsulfonylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC=C1S(=O)(=O)[C@H]1CN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 UCRKBUCWUKGLCR-IRLDBZIGSA-N 0.000 description 1
- JWCJEIGEQZVGPA-WBVHZDCISA-N (2s,4r)-4-(2-chlorophenyl)sulfonyl-n-(cyanomethyl)-1-(4-fluorobenzoyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(F)=CC=C1C(=O)N1[C@H](C(=O)NCC#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)Cl)C1 JWCJEIGEQZVGPA-WBVHZDCISA-N 0.000 description 1
- NLGQCCUHJTZXJP-APPZFPTMSA-N (2s,4r)-4-(2-chlorophenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1N[C@H](C(=O)O)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl NLGQCCUHJTZXJP-APPZFPTMSA-N 0.000 description 1
- BJTJCFVYBOCFRI-OLZOCXBDSA-N (2s,4r)-4-(4-chloro-2-methylphenyl)sulfonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC1=CC(Cl)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(O)=O)C1 BJTJCFVYBOCFRI-OLZOCXBDSA-N 0.000 description 1
- GUIHNPPBSJTXPY-OLZOCXBDSA-N (2s,4r)-4-(benzenesulfonyl)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@@H]1S(=O)(=O)C1=CC=CC=C1 GUIHNPPBSJTXPY-OLZOCXBDSA-N 0.000 description 1
- MREKQNRKNQCXGE-SJORKVTESA-N (2s,4r)-4-(benzenesulfonyl)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]pyrrolidine-2-carboxylic acid Chemical compound O=S([C@H]1CN([C@@H](C1)C(O)=O)C1=CC(=NN1C=1C=C(Cl)N=CC=1)C)(=O)C1=CC=CC=C1 MREKQNRKNQCXGE-SJORKVTESA-N 0.000 description 1
- FAIFWIRBNAVCIU-APPZFPTMSA-N (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]pyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C[C@H]1C(=O)O)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=NN=C(C(F)(F)F)S1 FAIFWIRBNAVCIU-APPZFPTMSA-N 0.000 description 1
- ACDZAASPTGKUOL-TUJLOAKASA-N (2s,4r)-4-[2-chloro-4-(1,1,1-trifluoropropan-2-yloxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OC(C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 ACDZAASPTGKUOL-TUJLOAKASA-N 0.000 description 1
- YOJLEQWVEYZJOF-ICSQTIAXSA-N (2s,4r)-4-[2-chloro-4-(1,1,1-trifluoropropan-2-yloxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-formylpyrrolidine-2-carboxamide Chemical compound ClC1=CC(OC(C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C=O)[C@H](C(=O)NC2(CC2)C#N)C1 YOJLEQWVEYZJOF-ICSQTIAXSA-N 0.000 description 1
- QOXLZGXUAPRKTK-VOHIISRTSA-N (2s,4r)-4-[2-chloro-4-(1,1,1-trifluoropropan-2-yloxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OC(C)C(F)(F)F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 QOXLZGXUAPRKTK-VOHIISRTSA-N 0.000 description 1
- CHRQVPQVEFAQSS-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-1-(1-cyanocyclopropanecarbonyl)-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C#N)[C@H](C(=O)NC2(CC2)C#N)C1 CHRQVPQVEFAQSS-ZBFHGGJFSA-N 0.000 description 1
- ZZPFJIHOYGDCLG-YPMHNXCESA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylic acid Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)NC1(C#N)CC1 ZZPFJIHOYGDCLG-YPMHNXCESA-N 0.000 description 1
- GYLWFGRIZHHMAX-BWKNWUBXSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-naphthalen-1-ylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C3=CC=CC=C3C=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 GYLWFGRIZHHMAX-BWKNWUBXSA-N 0.000 description 1
- XZGSOJZUTDACQO-NOZRDPDXSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-naphthalen-2-ylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=C3C=CC=CC3=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 XZGSOJZUTDACQO-NOZRDPDXSA-N 0.000 description 1
- UDHPZJBKBYGGEJ-VWNXMTODSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-phenylcyclohexanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CCCCC2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 UDHPZJBKBYGGEJ-VWNXMTODSA-N 0.000 description 1
- XSPQAJWHOFBUPZ-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-phenylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 XSPQAJWHOFBUPZ-CTNGQTDRSA-N 0.000 description 1
- ZUPRMXHTRPIAFR-JHIQODARSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2-difluorocyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2C(C2)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 ZUPRMXHTRPIAFR-JHIQODARSA-N 0.000 description 1
- VPGSEYRNCKDIEM-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2-dimethylpropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)NC1(C#N)CC1 VPGSEYRNCKDIEM-ZBFHGGJFSA-N 0.000 description 1
- FJQQMJINNDSFQB-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2-methylpropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)C)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)NC1(C#N)CC1 FJQQMJINNDSFQB-ZBFHGGJFSA-N 0.000 description 1
- LCHOSTGJSYGANB-BWKNWUBXSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2-naphthalen-1-yl-1,3-dioxolane-2-carbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(OCCO2)C=2C3=CC=CC=C3C=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 LCHOSTGJSYGANB-BWKNWUBXSA-N 0.000 description 1
- BWWPBJSYLFAHAW-LCLFBYRMSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2-phenylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2C(C2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 BWWPBJSYLFAHAW-LCLFBYRMSA-N 0.000 description 1
- GCIXULHRIUNKEG-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(3-methyloxetane-3-carbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C)COC1 GCIXULHRIUNKEG-ZBFHGGJFSA-N 0.000 description 1
- URHOJIYKMYEXEX-GGAORHGYSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(4-phenyloxane-4-carbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CCOCC2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 URHOJIYKMYEXEX-GGAORHGYSA-N 0.000 description 1
- NHDUUHBICRMNAZ-UTKZUKDTSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(3,4-dichlorophenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=C(Cl)C(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 NHDUUHBICRMNAZ-UTKZUKDTSA-N 0.000 description 1
- LCCVEVQLUOBJIY-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(4-fluorophenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=CC(F)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 LCCVEVQLUOBJIY-CTNGQTDRSA-N 0.000 description 1
- YUTSOPXEDLVJLW-IRLDBZIGSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(4-methylphenyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=CC(C)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C(=O)NC2(CC2)C#N)CC1 YUTSOPXEDLVJLW-IRLDBZIGSA-N 0.000 description 1
- HWSWSCBVIFMWDT-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-[3-(trifluoromethyl)phenyl]cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=C(C=CC=2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 HWSWSCBVIFMWDT-CTNGQTDRSA-N 0.000 description 1
- HEUDCMNHALYKCT-NOZRDPDXSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-[4-(1-methylpyrazol-4-yl)phenyl]cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=NN(C)C=C1C1=CC=C(C2(CC2)C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)Cl)C(=O)NC2(CC2)C#N)C=C1 HEUDCMNHALYKCT-NOZRDPDXSA-N 0.000 description 1
- BWXIDJRVNYUYDO-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-[4-(trifluoromethyl)phenyl]cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(=CC=2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 BWXIDJRVNYUYDO-CTNGQTDRSA-N 0.000 description 1
- IWHLYWUULRFAHQ-BEFAXECRSA-N (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[2-(trifluoromethyl)benzoyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C=2C(=CC=CC=2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 IWHLYWUULRFAHQ-BEFAXECRSA-N 0.000 description 1
- JLXNLZLBADWKGG-GGAORHGYSA-N (2s,4r)-4-[2-chloro-4-(2-methoxyethoxy)phenyl]sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(OCCOC)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 JLXNLZLBADWKGG-GGAORHGYSA-N 0.000 description 1
- QJJMZYIERZRWNX-VWNXMTODSA-N (2s,4r)-4-[2-chloro-4-(2-methylimidazol-1-yl)phenyl]sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound CC1=NC=CN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)C(Cl)=C1 QJJMZYIERZRWNX-VWNXMTODSA-N 0.000 description 1
- OBHSCZGAEWEMQT-HIFRSBDPSA-N (2s,4r)-4-[2-chloro-4-(3,3-difluoropyrrolidin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1C(F)(F)CCN1C1=CC=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(Cl)=C1 OBHSCZGAEWEMQT-HIFRSBDPSA-N 0.000 description 1
- PWJJWRKVZDOYFX-VPUSJEBWSA-N (2s,4r)-4-[2-chloro-4-(4-cyclopropylpiperazin-1-yl)phenyl]sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(=CC=2)N2CCN(CC2)C2CC2)Cl)C(=O)NC2(CC2)C#N)CC1 PWJJWRKVZDOYFX-VPUSJEBWSA-N 0.000 description 1
- JVPDQODOOWFDGL-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-(4-cyclopropylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CCN(CC1)C1CC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 JVPDQODOOWFDGL-CTNGQTDRSA-N 0.000 description 1
- IUKJOHLHTCEUOZ-MJGOQNOKSA-N (2s,4r)-4-[2-chloro-4-(4-ethylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-formylpyrrolidine-2-carboxamide Chemical compound C1CN(CC)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C=O)C(Cl)=C1 IUKJOHLHTCEUOZ-MJGOQNOKSA-N 0.000 description 1
- DOZIPINLUIDBCW-AEFFLSMTSA-N (2s,4r)-4-[2-chloro-4-(4-ethylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CN(CC)CCN1C1=CC=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(Cl)=C1 DOZIPINLUIDBCW-AEFFLSMTSA-N 0.000 description 1
- BWPNNSSQUSKEGH-NOZRDPDXSA-N (2s,4r)-4-[2-chloro-4-(4-methylpiperazin-1-yl)phenyl]sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C=2C=CC(Cl)=CC=2)C(Cl)=C1 BWPNNSSQUSKEGH-NOZRDPDXSA-N 0.000 description 1
- YAJMVNAZFUCHBP-MJGOQNOKSA-N (2s,4r)-4-[2-chloro-4-(4-methylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 YAJMVNAZFUCHBP-MJGOQNOKSA-N 0.000 description 1
- HXTPZEJZSYZRGK-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-(4-propan-2-ylpiperazin-1-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(C(C)C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 HXTPZEJZSYZRGK-CTNGQTDRSA-N 0.000 description 1
- VHBVWMZFWCTGER-AEFFLSMTSA-N (2s,4r)-4-[2-chloro-4-(6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1CC2=NN=CN2CC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 VHBVWMZFWCTGER-AEFFLSMTSA-N 0.000 description 1
- SYISASBGMLEOAO-ZBFHGGJFSA-N (2s,4r)-4-[2-chloro-4-(dimethylamino)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound ClC1=CC(N(C)C)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 SYISASBGMLEOAO-ZBFHGGJFSA-N 0.000 description 1
- VTYXDRCYBNTAHL-WBVHZDCISA-N (2s,4r)-4-[2-chloro-4-(oxetan-3-yloxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(OC2COC2)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 VTYXDRCYBNTAHL-WBVHZDCISA-N 0.000 description 1
- IVORTDKXJMRUMM-HIFRSBDPSA-N (2s,4r)-4-[2-chloro-4-(oxetan-3-yloxy)phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C=1C=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(Cl)=CC=1OC1COC1 IVORTDKXJMRUMM-HIFRSBDPSA-N 0.000 description 1
- OBFPJLHMXXWZTR-NDMJEZRESA-N (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxylic acid Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(O)=O)C1 OBFPJLHMXXWZTR-NDMJEZRESA-N 0.000 description 1
- HDSCZNUPELMQHT-LXZKKBNFSA-N (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(C)CC2)[C@H](C(=O)NC2(CC2)C#N)C1 HDSCZNUPELMQHT-LXZKKBNFSA-N 0.000 description 1
- DRDGLBWAZIDCCP-LXZKKBNFSA-N (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(2,2-dimethylpropanoyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C(C)(C)C)[C@H](C(=O)NC2(CC2)C#N)C1 DRDGLBWAZIDCCP-LXZKKBNFSA-N 0.000 description 1
- WUQGZVYSSFIIOL-MJGOQNOKSA-N (2s,4r)-4-[2-chloro-4-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(CC(F)(F)F)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 WUQGZVYSSFIIOL-MJGOQNOKSA-N 0.000 description 1
- BXCNBYVZFAJHFU-CTNGQTDRSA-N (2s,4r)-4-[2-chloro-4-[4-(2-methoxyethyl)piperazin-1-yl]phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(CCOC)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 BXCNBYVZFAJHFU-CTNGQTDRSA-N 0.000 description 1
- CWUCANDJGKBZMT-MJGOQNOKSA-N (2s,4r)-4-[2-chloro-4-[4-(trifluoromethyl)piperidin-1-yl]phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CC(C(F)(F)F)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 CWUCANDJGKBZMT-MJGOQNOKSA-N 0.000 description 1
- SEYLBDODYLSLAO-WBVHZDCISA-N (2s,4r)-4-[2-chloro-4-[4-(trifluoromethyl)piperidin-1-yl]phenyl]sulfonyl-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1CC(C(F)(F)F)CCN1C1=CC=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(Cl)=C1 SEYLBDODYLSLAO-WBVHZDCISA-N 0.000 description 1
- VTYGCLCKJSDZFA-MJGOQNOKSA-N (2s,4r)-4-[4-(2-chloropyridin-4-yl)-2-(trifluoromethyl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)C=1C=C(Cl)N=CC=1)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 VTYGCLCKJSDZFA-MJGOQNOKSA-N 0.000 description 1
- OLJRLIKARFEASI-AEFFLSMTSA-N (2s,4r)-4-[4-(2-chloropyridin-4-yl)-2-(trifluoromethyl)phenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)C=1C=C(Cl)N=CC=1)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 OLJRLIKARFEASI-AEFFLSMTSA-N 0.000 description 1
- NELXJZXFLCAEBH-CTNGQTDRSA-N (2s,4r)-4-[4-(4-tert-butylpiperazin-1-yl)-2-chlorophenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(C(C)(C)C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(Cl)=C1 NELXJZXFLCAEBH-CTNGQTDRSA-N 0.000 description 1
- AOIDEDCTPDKZHA-DGPALRBDSA-N (2s,4r)-4-[4-(4-tert-butylpiperazin-1-yl)-2-chlorophenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1CCC=1C=CC=CC=1)C)S(=O)(=O)C=1C(=CC(=CC=1)N1CCN(CC1)C(C)(C)C)Cl)NC1(C#N)CC1 AOIDEDCTPDKZHA-DGPALRBDSA-N 0.000 description 1
- BYUBUZHLADFRBV-VPUSJEBWSA-N (2s,4r)-4-[4-(4-tert-butylpiperazin-1-yl)-2-chlorophenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[5-methyl-2-(oxan-4-yl)pyrazol-3-yl]pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C1CCOCC1)C)S(=O)(=O)C=1C(=CC(=CC=1)N1CCN(CC1)C(C)(C)C)Cl)NC1(C#N)CC1 BYUBUZHLADFRBV-VPUSJEBWSA-N 0.000 description 1
- IBOFFKDHDZSGKY-GGAORHGYSA-N (2s,4r)-4-[4-(azetidin-1-yl)-2-chlorophenyl]sulfonyl-1-[1-(4-chlorophenyl)cyclopropanecarbonyl]-n-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1(C(=O)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC(=CC=2)N2CCC2)Cl)C(=O)NC2(CC2)C#N)CC1 IBOFFKDHDZSGKY-GGAORHGYSA-N 0.000 description 1
- LAFUEBKKICJHMJ-ZVDOUQERSA-N (2s,4r)-4-[4-[(8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl]-2-chlorophenyl]sulfonyl-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)N1C[C@@H]2CCCN2CC1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 LAFUEBKKICJHMJ-ZVDOUQERSA-N 0.000 description 1
- LVTJMRBFJPSXIF-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(1,5-dimethylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CN1C(C)=CC(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=N1 LVTJMRBFJPSXIF-ZBFHGGJFSA-N 0.000 description 1
- DURXBXOHDRWFKW-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 DURXBXOHDRWFKW-HIFRSBDPSA-N 0.000 description 1
- IXOVAIPZJWZMRR-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)-4-[4-(1-methylpyrazol-4-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=NN(C)C=C1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(C)CC2)C(C(F)(F)F)=C1 IXOVAIPZJWZMRR-MJGOQNOKSA-N 0.000 description 1
- YQOUMYWWGFBAQQ-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)-4-[4-(2-methylpyridin-4-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=NC(C)=CC(C=2C=C(C(=CC=2)S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(C)CC2)C(F)(F)F)=C1 YQOUMYWWGFBAQQ-CTNGQTDRSA-N 0.000 description 1
- BMGRMRGRZZSPOH-QUCCMNQESA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(1-methylcyclopropanecarbonyl)-4-[4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(C)CC2)C(C(F)(F)F)=C1 BMGRMRGRZZSPOH-QUCCMNQESA-N 0.000 description 1
- ILGZRAMXTLPBSV-PWSUYJOCSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2,2,2-trifluoroacetyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 ILGZRAMXTLPBSV-PWSUYJOCSA-N 0.000 description 1
- DDKTYJJYOZPCDP-YPMHNXCESA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2,2,3,3,3-pentafluoropropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(CC(F)(F)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 DDKTYJJYOZPCDP-YPMHNXCESA-N 0.000 description 1
- CSBZCSUQYJOROT-ZBFHGGJFSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2,2-dimethylpropanoyl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)C(F)(F)F)NC1(C#N)CC1 CSBZCSUQYJOROT-ZBFHGGJFSA-N 0.000 description 1
- HWMTWIDRVOILOR-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(2,2-dimethylpropanoyl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)C(C)(C)C)S(=O)(=O)C=1C(=CC(F)=CC=1)C(F)(F)F)NC1(C#N)CC1 HWMTWIDRVOILOR-HIFRSBDPSA-N 0.000 description 1
- SXPRWFKEFGOTHL-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(4-methoxyphenyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=CC(OC)=CC=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 SXPRWFKEFGOTHL-MJGOQNOKSA-N 0.000 description 1
- JAWKSAGTDLZHEH-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CC(C)N1N=C(C)C=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)C(F)(F)F)C1 JAWKSAGTDLZHEH-MJGOQNOKSA-N 0.000 description 1
- PFPPDMYWABQOTH-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-(cyclohexanecarbonyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2CCCCC2)[C@H](C(=O)NC2(CC2)C#N)C1 PFPPDMYWABQOTH-AEFFLSMTSA-N 0.000 description 1
- XYLZHHKIMWFHNK-OCCSQVGLSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[1-(trifluoromethyl)cyclopropanecarbonyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 XYLZHHKIMWFHNK-OCCSQVGLSA-N 0.000 description 1
- QBMXZEQBMRNRIE-XLIONFOSSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[1-methyl-5-(oxan-4-yl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound CN1N=C(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)C=C1C1CCOCC1 QBMXZEQBMRNRIE-XLIONFOSSA-N 0.000 description 1
- IPBOHWRTRLEBBZ-IRLDBZIGSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[2-(2,6-dimethylpyridin-4-yl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=C(C)N=C(C)C=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 IPBOHWRTRLEBBZ-IRLDBZIGSA-N 0.000 description 1
- HSEMOQSMMUHGHR-IRLDBZIGSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[2-(3-methoxyphenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound COC1=CC=CC(N2C(=CC(C)=N2)N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=C1 HSEMOQSMMUHGHR-IRLDBZIGSA-N 0.000 description 1
- JLMSBUUSEMMESH-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[2-(4-fluorophenyl)-5-methylpyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(F)=CC=1)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 JLMSBUUSEMMESH-CTNGQTDRSA-N 0.000 description 1
- DQMNLDKDJDNRIO-IOTAOYMUSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[4-(trifluoromethyl)cyclohexanecarbonyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1CC(C(F)(F)F)CCC1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 DQMNLDKDJDNRIO-IOTAOYMUSA-N 0.000 description 1
- ABAHIJBXIPTUIM-OFNKIYASSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-cyclopropyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1N1C(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=CC(C2CC2)=N1 ABAHIJBXIPTUIM-OFNKIYASSA-N 0.000 description 1
- LMYTWVGHVGBNJA-CTNGQTDRSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 LMYTWVGHVGBNJA-CTNGQTDRSA-N 0.000 description 1
- PJOHPAGTHPNZHZ-IRLDBZIGSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C1=CC(=NN1C=1C=CC(=CC=1)C(F)(F)F)C)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)C(F)(F)F)NC1(C#N)CC1 PJOHPAGTHPNZHZ-IRLDBZIGSA-N 0.000 description 1
- JILQFLUJFOCZIX-YPMHNXCESA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-formyl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C=O)[C@H](C(=O)NC2(CC2)C#N)C1 JILQFLUJFOCZIX-YPMHNXCESA-N 0.000 description 1
- NNEAVFLHNXAWDV-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-phenyl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 NNEAVFLHNXAWDV-AEFFLSMTSA-N 0.000 description 1
- UTUGQIBUHNZZII-OCCSQVGLSA-N (2s,4r)-n-(1-cyanocyclopropyl)-1-propanoyl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 UTUGQIBUHNZZII-OCCSQVGLSA-N 0.000 description 1
- BFCWGXAKVCCUKL-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 BFCWGXAKVCCUKL-HIFRSBDPSA-N 0.000 description 1
- GYGHISVPNZVNCA-QUCCMNQESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(1-phenylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound ClC1=CC(Cl)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C=2C=CC=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 GYGHISVPNZVNCA-QUCCMNQESA-N 0.000 description 1
- KEJPJJOEXOCIPH-SOGVLRHJSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(2,2-difluorocyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound FC1(F)CC1C(=O)N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)C1 KEJPJJOEXOCIPH-SOGVLRHJSA-N 0.000 description 1
- KVYICVQIGPZMGO-KDOFPFPSSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(2-nitrophenyl)pyrrolidine-2-carboxamide Chemical compound [O-][N+](=O)C1=CC=CC=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)C1 KVYICVQIGPZMGO-KDOFPFPSSA-N 0.000 description 1
- HYNNIWJGEZLQIF-YPMHNXCESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC(F)(F)F)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)NC1(C#N)CC1 HYNNIWJGEZLQIF-YPMHNXCESA-N 0.000 description 1
- FFBJSNDGZVCJON-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-[1-(trifluoromethyl)cyclobutanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CCC1 FFBJSNDGZVCJON-HIFRSBDPSA-N 0.000 description 1
- OTURMIBYLZGRGD-OCCSQVGLSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)C(=O)NC1(CC1)C#N)C(=O)C1(C(F)(F)F)CC1 OTURMIBYLZGRGD-OCCSQVGLSA-N 0.000 description 1
- SAXXUFDIJRCLFF-CJNGLKHVSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-dichlorophenyl)sulfonyl-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CN=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC(Cl)=CC=2)Cl)C1 SAXXUFDIJRCLFF-CJNGLKHVSA-N 0.000 description 1
- NPGYABVWQBIPTJ-PWSUYJOCSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,4-difluorophenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 NPGYABVWQBIPTJ-PWSUYJOCSA-N 0.000 description 1
- DRXQDYOCYDGAOA-SKDRFNHKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2,6-dichlorophenyl)sulfonylpyrrolidine-2-carboxamide Chemical compound ClC1=CC=CC(Cl)=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 DRXQDYOCYDGAOA-SKDRFNHKSA-N 0.000 description 1
- ZDYZVGJRYGGZSB-DHXVBOOMSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-(2-methylpropylsulfonyl)pyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.C1[C@@H](S(=O)(=O)CC(C)C)CN[C@@H]1C(=O)NC1(C#N)CC1 ZDYZVGJRYGGZSB-DHXVBOOMSA-N 0.000 description 1
- XLDBVCNDEZKPHY-YPMHNXCESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-(3,3,3-trifluoropropanoyl)pyrrolidine-2-carboxamide Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)CC(F)(F)F)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 XLDBVCNDEZKPHY-YPMHNXCESA-N 0.000 description 1
- SEXOQCVMHMBHLP-OCCSQVGLSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[2-(trifluoromethyl)pyrimidin-4-yl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=NC=CC(N2[C@@H](C[C@H](C2)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C(=O)NC2(CC2)C#N)=N1 SEXOQCVMHMBHLP-OCCSQVGLSA-N 0.000 description 1
- KXYZKSPGWZDZAC-CJNGLKHVSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CN=C1N1[C@H](C(=O)NC2(CC2)C#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 KXYZKSPGWZDZAC-CJNGLKHVSA-N 0.000 description 1
- ADMQZTMBHHMHME-PWSUYJOCSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 ADMQZTMBHHMHME-PWSUYJOCSA-N 0.000 description 1
- KXAAIORSMACJSI-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(1-methylpyrazol-4-yl)-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=NN(C)C=C1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(C(F)(F)F)=C1 KXAAIORSMACJSI-AEFFLSMTSA-N 0.000 description 1
- ZKPUZRFJTJCJBI-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)C2(CC2)C(F)(F)F)[C@H](C(=O)NC2(CC2)C#N)C1 ZKPUZRFJTJCJBI-HIFRSBDPSA-N 0.000 description 1
- QRSNPNAFVHBZBU-YPMHNXCESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 QRSNPNAFVHBZBU-YPMHNXCESA-N 0.000 description 1
- JDLLWNDQSVLQSJ-UTKZUKDTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2,4-difluorophenyl)-2-(trifluoromethyl)phenyl]sulfonyl-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)C=1C(=CC(F)=CC=1)F)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 JDLLWNDQSVLQSJ-UTKZUKDTSA-N 0.000 description 1
- CGVVOGJZIKKEMV-UZLBHIALSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2,4-difluorophenyl)-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound FC1=CC(F)=CC=C1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(C(F)(F)F)=C1 CGVVOGJZIKKEMV-UZLBHIALSA-N 0.000 description 1
- SSTXXMXPTWIRHH-XMZRARIVSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2-methylimidazol-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.CC1=NC=CN1C1=CC=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(C(F)(F)F)=C1 SSTXXMXPTWIRHH-XMZRARIVSA-N 0.000 description 1
- CDBYZSRUFZXRLK-QUCCMNQESA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2-methylpyridin-4-yl)-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1=NC(C)=CC(C=2C=C(C(=CC=2)S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(F)(F)F)=C1 CDBYZSRUFZXRLK-QUCCMNQESA-N 0.000 description 1
- YYEGZFCUJQVTFN-PBCQUBLHSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2-oxopyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1C(CCC1)=O)NC1(C#N)CC1 YYEGZFCUJQVTFN-PBCQUBLHSA-N 0.000 description 1
- JLSOPGLLHIQCOS-VDWUQFQWSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(2-phenylimidazol-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1C(=NC=C1)C=1C=CC=CC=1)NC1(C#N)CC1 JLSOPGLLHIQCOS-VDWUQFQWSA-N 0.000 description 1
- CPZUZAYAARXNSR-PBCQUBLHSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(3,3-difluoropyrrolidin-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1CC(F)(F)CC1)NC1(C#N)CC1 CPZUZAYAARXNSR-PBCQUBLHSA-N 0.000 description 1
- NYCJKPQCFKDWCQ-PBCQUBLHSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(3-oxomorpholin-4-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1C(COCC1)=O)NC1(C#N)CC1 NYCJKPQCFKDWCQ-PBCQUBLHSA-N 0.000 description 1
- HAGIKOLXYJUYTG-MJGOQNOKSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)phenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)C2(CC2)C(F)(F)F)C(C(F)(F)F)=C1 HAGIKOLXYJUYTG-MJGOQNOKSA-N 0.000 description 1
- RSQBELIRLIMWBF-KALLACGZSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC=C(S(=O)(=O)[C@@H]2C[C@H](NC2)C(=O)NC2(CC2)C#N)C(C(F)(F)F)=C1 RSQBELIRLIMWBF-KALLACGZSA-N 0.000 description 1
- MBOSREWWGNVEHF-AEFFLSMTSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-cyclopropyl-2-(trifluoromethyl)phenyl]sulfonyl-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(=CC=1)C1CC1)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 MBOSREWWGNVEHF-AEFFLSMTSA-N 0.000 description 1
- VPTODBPUWCRZDS-HIFRSBDPSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-(1-methylcyclopropanecarbonyl)pyrrolidine-2-carboxamide Chemical compound N1([C@@H](C[C@H](C1)S(=O)(=O)C=1C(=CC(F)=CC=1)C(F)(F)F)C(=O)NC1(CC1)C#N)C(=O)C1(C)CC1 VPTODBPUWCRZDS-HIFRSBDPSA-N 0.000 description 1
- FZZLPTNBWNVWAY-PWSUYJOCSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC(F)=CC=C1S(=O)(=O)[C@@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 FZZLPTNBWNVWAY-PWSUYJOCSA-N 0.000 description 1
- FPCSRCUUJLTQPB-PBCQUBLHSA-N (2s,4r)-n-(1-cyanocyclopropyl)-4-[4-pyrazol-1-yl-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NC[C@@H](C1)S(=O)(=O)C1=CC=C(C=C1C(F)(F)F)N1N=CC=C1)NC1(C#N)CC1 FPCSRCUUJLTQPB-PBCQUBLHSA-N 0.000 description 1
- QKDGDTOEHPZWBN-WBVHZDCISA-N (2s,4r)-n-(cyanomethyl)-1-(1-methylpiperidine-4-carbonyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1CN(C)CCC1C(=O)N1[C@H](C(=O)NCC#N)C[C@@H](S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)C1 QKDGDTOEHPZWBN-WBVHZDCISA-N 0.000 description 1
- HHDQVBSXYDRQGD-IMJSIDKUSA-N (2s,4s)-4-hydroxypyrrolidine-1,2-dicarboxylic acid Chemical compound O[C@H]1C[C@@H](C(O)=O)N(C(O)=O)C1 HHDQVBSXYDRQGD-IMJSIDKUSA-N 0.000 description 1
- ADMQZTMBHHMHME-JQWIXIFHSA-N (2s,4s)-n-(1-cyanocyclopropyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1C[C@@H](C(=O)NC2(CC2)C#N)NC1 ADMQZTMBHHMHME-JQWIXIFHSA-N 0.000 description 1
- GFPJLZASIVURDY-UHFFFAOYSA-N (3-chlorophenyl)hydrazine Chemical compound NNC1=CC=CC(Cl)=C1 GFPJLZASIVURDY-UHFFFAOYSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- WZNQBRBCWIJGDE-MJGOQNOKSA-N (4-chlorophenyl) (2s,4r)-4-[2-chloro-4-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound ClC1=CC(OCC(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC=2C=CC(Cl)=CC=2)[C@H](C(=O)NC2(CC2)C#N)C1 WZNQBRBCWIJGDE-MJGOQNOKSA-N 0.000 description 1
- RYWGPCLTVXMMHO-UHFFFAOYSA-N (4-chlorophenyl) carbonochloridate Chemical compound ClC(=O)OC1=CC=C(Cl)C=C1 RYWGPCLTVXMMHO-UHFFFAOYSA-N 0.000 description 1
- MSBGPEACXKBQSX-UHFFFAOYSA-N (4-fluorophenyl) carbonochloridate Chemical compound FC1=CC=C(OC(Cl)=O)C=C1 MSBGPEACXKBQSX-UHFFFAOYSA-N 0.000 description 1
- ZXBMIRYQUFQQNX-UHFFFAOYSA-N (4-fluorophenyl)hydrazine Chemical compound NNC1=CC=C(F)C=C1 ZXBMIRYQUFQQNX-UHFFFAOYSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- SGEOBUJTURUUJE-UHFFFAOYSA-N (6-propan-2-yloxypyridin-3-yl)boronic acid Chemical compound CC(C)OC1=CC=C(B(O)O)C=N1 SGEOBUJTURUUJE-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- BTWNEJOURYOHME-UHFFFAOYSA-N 1,3-thiazol-2-ylhydrazine Chemical compound NNC1=NC=CS1 BTWNEJOURYOHME-UHFFFAOYSA-N 0.000 description 1
- VNBCEUVYNYCYBW-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1(C(=O)O)CC1 VNBCEUVYNYCYBW-UHFFFAOYSA-N 0.000 description 1
- MYDCJGVBYNDHIC-UHFFFAOYSA-N 1-(3-bromophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=CC(Br)=CC=1C1(C(=O)O)CC1 MYDCJGVBYNDHIC-UHFFFAOYSA-N 0.000 description 1
- QUIQAEWPDRXLFW-UHFFFAOYSA-N 1-(3-chlorophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=CC(Cl)=CC=1C1(C(=O)O)CC1 QUIQAEWPDRXLFW-UHFFFAOYSA-N 0.000 description 1
- BYJIXWOWTNEVFO-UHFFFAOYSA-N 1-(4-bromophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(Br)C=CC=1C1(C(=O)O)CC1 BYJIXWOWTNEVFO-UHFFFAOYSA-N 0.000 description 1
- UPNXUJXIIZGXLQ-UHFFFAOYSA-N 1-(4-chlorophenyl)cyclohexane-1-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C1(C(=O)O)CCCCC1 UPNXUJXIIZGXLQ-UHFFFAOYSA-N 0.000 description 1
- QJNFJEMGWIQMJT-UHFFFAOYSA-N 1-(4-chlorophenyl)cyclopentane-1-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C1(C(=O)O)CCCC1 QJNFJEMGWIQMJT-UHFFFAOYSA-N 0.000 description 1
- NGVPHOXWSFIYNV-UHFFFAOYSA-N 1-(4-fluorophenyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CC1 NGVPHOXWSFIYNV-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- DSKCOVBHIFAJRI-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1(C(O)=O)CC1 DSKCOVBHIFAJRI-UHFFFAOYSA-N 0.000 description 1
- YMJJHWPAULQWGR-UHFFFAOYSA-N 1-aminocyclobutane-1-carbonitrile;hydrochloride Chemical compound Cl.N#CC1(N)CCC1 YMJJHWPAULQWGR-UHFFFAOYSA-N 0.000 description 1
- UZDHDPDJHBPQTQ-UHFFFAOYSA-N 1-aminocyclohexane-1-carbonitrile;hydron;chloride Chemical compound Cl.N#CC1(N)CCCCC1 UZDHDPDJHBPQTQ-UHFFFAOYSA-N 0.000 description 1
- CIARJFDNBQFOJK-UHFFFAOYSA-N 1-aminocyclopropane-1-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound N#CC1(N)CC1.OC(=O)C(F)(F)F CIARJFDNBQFOJK-UHFFFAOYSA-N 0.000 description 1
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
- KSJJMSKNZVXAND-UHFFFAOYSA-N 1-cyanocyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C#N)CC1 KSJJMSKNZVXAND-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- UCNGGGYMLHAMJG-UHFFFAOYSA-N 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(C)C=C1B1OC(C)(C)C(C)(C)O1 UCNGGGYMLHAMJG-UHFFFAOYSA-N 0.000 description 1
- BMRGZUQRUPQDIM-OCCSQVGLSA-N 1-o-tert-butyl 2-o-ethyl (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OCC)C[C@H]1SC1=CC=CC=C1C(F)(F)F BMRGZUQRUPQDIM-OCCSQVGLSA-N 0.000 description 1
- AGOVRPUNRLUCQN-OCCSQVGLSA-N 1-o-tert-butyl 2-o-ethyl (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OCC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F AGOVRPUNRLUCQN-OCCSQVGLSA-N 0.000 description 1
- GVRCVZAUNGAWGN-ZFWWWQNUSA-N 1-o-tert-butyl 2-o-ethyl (2s,4s)-4-(3-nitrophenyl)sulfonyloxypyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OCC)C[C@@H]1OS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 GVRCVZAUNGAWGN-ZFWWWQNUSA-N 0.000 description 1
- MNMDZSAWTQOEHX-IUCAKERBSA-N 1-o-tert-butyl 2-o-ethyl (2s,4s)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound CCOC(=O)[C@@H]1C[C@H](O)CN1C(=O)OC(C)(C)C MNMDZSAWTQOEHX-IUCAKERBSA-N 0.000 description 1
- ZPAMHUFTWHJPCQ-NJNPRVFISA-N 1-o-tert-butyl 2-o-methyl (2r,4s,5r)-5-(4-fluorophenyl)-2-(2-methylpropyl)-4-methylsulfonylpyrrolidine-1,2-dicarboxylate Chemical compound CC(C)(C)OC(=O)N1[C@](C(=O)OC)(CC(C)C)C[C@H](S(C)(=O)=O)[C@H]1C1=CC=C(F)C=C1 ZPAMHUFTWHJPCQ-NJNPRVFISA-N 0.000 description 1
- UCJGQLRJVMHJML-PWSUYJOCSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(2,3-dichlorophenyl)sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=CC(Cl)=C1Cl UCJGQLRJVMHJML-PWSUYJOCSA-N 0.000 description 1
- IFDLZLIMBFGNNA-PWSUYJOCSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(2,3-dichlorophenyl)sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC(Cl)=C1Cl IFDLZLIMBFGNNA-PWSUYJOCSA-N 0.000 description 1
- KEVRTIKXLXIQHO-CABCVRRESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(2,4-dimethylphenyl)sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=C(C)C=C1C KEVRTIKXLXIQHO-CABCVRRESA-N 0.000 description 1
- NEBKCASWMOAVCV-CABCVRRESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(2,4-dimethylphenyl)sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(C)C=C1C NEBKCASWMOAVCV-CABCVRRESA-N 0.000 description 1
- UFFSVOAAHRHKOF-YPMHNXCESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(2-chlorophenyl)sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=CC=C1Cl UFFSVOAAHRHKOF-YPMHNXCESA-N 0.000 description 1
- YCMGADKVZQSWMK-KGLIPLIRSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(4-chloro-2-methylphenyl)sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=C(Cl)C=C1C YCMGADKVZQSWMK-KGLIPLIRSA-N 0.000 description 1
- QQHXYAPVCUWEEX-KGLIPLIRSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-(4-chloro-2-methylphenyl)sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(Cl)C=C1C QQHXYAPVCUWEEX-KGLIPLIRSA-N 0.000 description 1
- CIAHXJHTTOCKHE-YPMHNXCESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=CC=C1C(F)(F)F CIAHXJHTTOCKHE-YPMHNXCESA-N 0.000 description 1
- ILNHHDVWOSHWFS-YPMHNXCESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F ILNHHDVWOSHWFS-YPMHNXCESA-N 0.000 description 1
- JYWGADRJQWPZNG-YPMHNXCESA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=C(F)C=C1C(F)(F)F JYWGADRJQWPZNG-YPMHNXCESA-N 0.000 description 1
- PHQKGCAXKMOGLR-KGLIPLIRSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-phenylsulfanylpyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@H]1SC1=CC=CC=C1 PHQKGCAXKMOGLR-KGLIPLIRSA-N 0.000 description 1
- UOMKQRSPIYBONY-UHFFFAOYSA-N 1-pyridin-4-ylcyclopropane-1-carboxylic acid Chemical compound C=1C=NC=CC=1C1(C(=O)O)CC1 UOMKQRSPIYBONY-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- ODMMNALOCMNQJZ-UHFFFAOYSA-N 1H-pyrrolizine Chemical compound C1=CC=C2CC=CN21 ODMMNALOCMNQJZ-UHFFFAOYSA-N 0.000 description 1
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 1
- RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 1
- PFKSLFZFBCIJOI-UHFFFAOYSA-N 2,2-difluoro-2-phenylacetic acid Chemical compound OC(=O)C(F)(F)C1=CC=CC=C1 PFKSLFZFBCIJOI-UHFFFAOYSA-N 0.000 description 1
- KMLMOVWSQPHQME-UHFFFAOYSA-N 2,2-difluorocyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1(F)F KMLMOVWSQPHQME-UHFFFAOYSA-N 0.000 description 1
- NKULBUOBGILEAR-UHFFFAOYSA-N 2,2-difluoroethyl trifluoromethanesulfonate Chemical compound FC(F)COS(=O)(=O)C(F)(F)F NKULBUOBGILEAR-UHFFFAOYSA-N 0.000 description 1
- QGRKONUHHGBHRB-UHFFFAOYSA-N 2,3-dichlorobenzenethiol Chemical compound SC1=CC=CC(Cl)=C1Cl QGRKONUHHGBHRB-UHFFFAOYSA-N 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- BICHBFCGCJNCAT-UHFFFAOYSA-N 2,4-difluorobenzenethiol Chemical compound FC1=CC=C(S)C(F)=C1 BICHBFCGCJNCAT-UHFFFAOYSA-N 0.000 description 1
- AMNLXDDJGGTIPL-UHFFFAOYSA-N 2,4-dimethylbenzenethiol Chemical compound CC1=CC=C(S)C(C)=C1 AMNLXDDJGGTIPL-UHFFFAOYSA-N 0.000 description 1
- JBISHCXLCGVPGW-UHFFFAOYSA-N 2,6-dichlorobenzenethiol Chemical compound SC1=C(Cl)C=CC=C1Cl JBISHCXLCGVPGW-UHFFFAOYSA-N 0.000 description 1
- SSFDAZXGUKDEAH-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=C(Cl)C=C1 SSFDAZXGUKDEAH-UHFFFAOYSA-N 0.000 description 1
- SLWAKPZBHUGHNQ-UHFFFAOYSA-N 2-(cyclopropylamino)acetonitrile;hydrochloride Chemical compound Cl.N#CCNC1CC1 SLWAKPZBHUGHNQ-UHFFFAOYSA-N 0.000 description 1
- CIIRSPLZNQRPGX-UHFFFAOYSA-N 2-(trifluoromethoxy)benzenethiol Chemical compound FC(F)(F)OC1=CC=CC=C1S CIIRSPLZNQRPGX-UHFFFAOYSA-N 0.000 description 1
- ABROBCBIIWHVNS-UHFFFAOYSA-N 2-Ethylbenzenethiol Chemical compound CCC1=CC=CC=C1S ABROBCBIIWHVNS-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- UFPIFDIPNZPHQK-UHFFFAOYSA-N 2-amino-2-cyclopropylacetonitrile Chemical compound N#CC(N)C1CC1 UFPIFDIPNZPHQK-UHFFFAOYSA-N 0.000 description 1
- XJKSATAZLNMPPO-UHFFFAOYSA-N 2-amino-2-cyclopropylacetonitrile;hydrochloride Chemical compound Cl.N#CC(N)C1CC1 XJKSATAZLNMPPO-UHFFFAOYSA-N 0.000 description 1
- RWPZHHGTDNTPFY-UHFFFAOYSA-N 2-amino-2-methylpropanenitrile;hydrochloride Chemical compound Cl.CC(C)(N)C#N RWPZHHGTDNTPFY-UHFFFAOYSA-N 0.000 description 1
- JTIHSSVKTWPPHI-UHFFFAOYSA-N 2-amino-2-phenylacetonitrile Chemical compound N#CC(N)C1=CC=CC=C1 JTIHSSVKTWPPHI-UHFFFAOYSA-N 0.000 description 1
- KUAPPJSILOMQPC-UHFFFAOYSA-N 2-chloro-4-fluorobenzenethiol Chemical compound FC1=CC=C(S)C(Cl)=C1 KUAPPJSILOMQPC-UHFFFAOYSA-N 0.000 description 1
- MNURPFVONZPVLA-UHFFFAOYSA-N 2-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1Cl MNURPFVONZPVLA-UHFFFAOYSA-N 0.000 description 1
- PWOBDMNCYMQTCE-UHFFFAOYSA-N 2-chlorobenzenethiol Chemical compound SC1=CC=CC=C1Cl PWOBDMNCYMQTCE-UHFFFAOYSA-N 0.000 description 1
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 1
- YSEFYOVWKJXNCH-UHFFFAOYSA-N 2-methoxyacetaldehyde Chemical compound COCC=O YSEFYOVWKJXNCH-UHFFFAOYSA-N 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- XAEBTCPOZVEMHR-UHFFFAOYSA-N 2-methylpropan-2-ol;potassium Chemical compound [K].CC(C)(C)O XAEBTCPOZVEMHR-UHFFFAOYSA-N 0.000 description 1
- ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 description 1
- FUOZJYASZOSONT-UHFFFAOYSA-N 2-propan-2-yl-1h-imidazole Chemical compound CC(C)C1=NC=CN1 FUOZJYASZOSONT-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- QLHMHPBDSYKXRI-UHFFFAOYSA-N 3,3,3-trifluoro-2-methylpropanal Chemical compound O=CC(C)C(F)(F)F QLHMHPBDSYKXRI-UHFFFAOYSA-N 0.000 description 1
- UTMIEQASUFFADK-UHFFFAOYSA-N 3,3,3-trifluoropropanal Chemical compound FC(F)(F)CC=O UTMIEQASUFFADK-UHFFFAOYSA-N 0.000 description 1
- KVTUSMPNLUCCQO-UHFFFAOYSA-N 3,3-difluoropyrrolidine Chemical compound FC1(F)CCNC1 KVTUSMPNLUCCQO-UHFFFAOYSA-N 0.000 description 1
- YYVPZQADFREIFR-UHFFFAOYSA-N 3,3-difluoropyrrolidine;hydrochloride Chemical class [Cl-].FC1(F)CC[NH2+]C1 YYVPZQADFREIFR-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- QZWIXLPWMGHDDD-UHFFFAOYSA-N 3-methyl-1h-pyridazin-6-one Chemical compound CC1=CC=C(O)N=N1 QZWIXLPWMGHDDD-UHFFFAOYSA-N 0.000 description 1
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 1
- OABUKBBBSMNNPM-UHFFFAOYSA-N 4,4-difluoropiperidin-1-ium;chloride Chemical class Cl.FC1(F)CCNCC1 OABUKBBBSMNNPM-UHFFFAOYSA-N 0.000 description 1
- RBLUPADGGYJWQJ-UHFFFAOYSA-N 4-(benzenesulfonyl)-5-(4-tert-butylphenyl)pyrrolidine-2-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1C(S(=O)(=O)C=2C=CC=CC=2)CC(C(O)=O)N1 RBLUPADGGYJWQJ-UHFFFAOYSA-N 0.000 description 1
- LMEAZIIFLVDISW-UHFFFAOYSA-N 4-(trifluoromethyl)cyclohexane-1-carboxylic acid Chemical compound OC(=O)C1CCC(C(F)(F)F)CC1 LMEAZIIFLVDISW-UHFFFAOYSA-N 0.000 description 1
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- YFXYEMZYOMNQLD-UHFFFAOYSA-N 4-bromo-2-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC(Br)=CC=C1S(Cl)(=O)=O YFXYEMZYOMNQLD-UHFFFAOYSA-N 0.000 description 1
- OVEGSCLVOXWLIV-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=NC=CC(Cl)=N1 OVEGSCLVOXWLIV-UHFFFAOYSA-N 0.000 description 1
- YIUPEFSJLWXHJR-UHFFFAOYSA-N 4-chloro-2-methylbenzenethiol Chemical compound CC1=CC(Cl)=CC=C1S YIUPEFSJLWXHJR-UHFFFAOYSA-N 0.000 description 1
- CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 1
- XXNOGQJZAOXWAQ-UHFFFAOYSA-N 4-chlorophenylhydrazine Chemical compound NNC1=CC=C(Cl)C=C1 XXNOGQJZAOXWAQ-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- XEJRCDGGVWETQJ-UHFFFAOYSA-N 4-imidazol-1-ylbenzenethiol Chemical compound C1=CC(S)=CC=C1N1C=NC=C1 XEJRCDGGVWETQJ-UHFFFAOYSA-N 0.000 description 1
- QTCKWXKCCGWABX-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;2-methylpropylhydrazine Chemical compound CC(C)CNN.CC1=CC=C(S(O)(=O)=O)C=C1 QTCKWXKCCGWABX-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- UNQYAAAWKOOBFQ-UHFFFAOYSA-N 7-[(4-chlorophenyl)methyl]-8-[4-chloro-3-(trifluoromethoxy)phenoxy]-1-(3-hydroxypropyl)-3-methylpurine-2,6-dione Chemical compound C=1C=C(Cl)C=CC=1CN1C=2C(=O)N(CCCO)C(=O)N(C)C=2N=C1OC1=CC=C(Cl)C(OC(F)(F)F)=C1 UNQYAAAWKOOBFQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000036490 Arterial inflammations Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- IEODLAWHMKMWRM-UHFFFAOYSA-N C(#N)C1(CC1)NC(=O)C1N(CCC1)C(=O)C1CC1 Chemical compound C(#N)C1(CC1)NC(=O)C1N(CCC1)C(=O)C1CC1 IEODLAWHMKMWRM-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940122805 Cathepsin S inhibitor Drugs 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- BRMCXWZOOYYFJR-SUHUHFCYSA-N ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(O)=O)C1 Chemical compound ClC1=CC(O[C@@H](C)C(F)(F)F)=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C(O)=O)C1 BRMCXWZOOYYFJR-SUHUHFCYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 241001137251 Corvidae Species 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 102000043859 Dynamin Human genes 0.000 description 1
- 108700021058 Dynamin Proteins 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 240000007839 Kleinhovia hospita Species 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical class [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 208000034827 Neointima Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- FZFJMXVWMWZYKA-JQWIXIFHSA-N O=C([C@@H]1C[C@@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 Chemical compound O=C([C@@H]1C[C@@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC1(C#N)CC1 FZFJMXVWMWZYKA-JQWIXIFHSA-N 0.000 description 1
- LGGSVEVTIOBIRJ-HIFRSBDPSA-N O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1CC(F)(F)CC1)Cl)NC1(C#N)CC1 Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1CC(F)(F)CC1)Cl)NC1(C#N)CC1 LGGSVEVTIOBIRJ-HIFRSBDPSA-N 0.000 description 1
- YUBXGRXZSKLEED-WBVHZDCISA-N O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1CCC(CC1)C(F)(F)F)Cl)NC1(C#N)CC1 Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(=CC=1)N1CCC(CC1)C(F)(F)F)Cl)NC1(C#N)CC1 YUBXGRXZSKLEED-WBVHZDCISA-N 0.000 description 1
- BOQQOFWXTZAJDP-MJGOQNOKSA-N O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(OCCN2CCCCC2)=CC=1)Cl)NC1(C#N)CC1 Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)O)S(=O)(=O)C=1C(=CC(OCCN2CCCCC2)=CC=1)Cl)NC1(C#N)CC1 BOQQOFWXTZAJDP-MJGOQNOKSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 101150024701 PPH3 gene Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 101000770223 Synechocystis sp. (strain PCC 6803 / Kazusa) Uncharacterized methyltransferase sll1242 Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000005475 Vascular calcification Diseases 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000005219 aminonitrile group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- GHIXWEZZNMAQFD-HNCPQSOCSA-N benzyl (2r)-4,4-difluoropyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.C1C(F)(F)CN[C@H]1C(=O)OCC1=CC=CC=C1 GHIXWEZZNMAQFD-HNCPQSOCSA-N 0.000 description 1
- VVCLBQFBKZQOAF-NSHDSACASA-N benzyl (2s)-pyrrolidine-2-carboxylate Chemical compound O=C([C@H]1NCCC1)OCC1=CC=CC=C1 VVCLBQFBKZQOAF-NSHDSACASA-N 0.000 description 1
- MLMWXEYPQVNNNE-UHFFFAOYSA-N benzyl 1-(benzenesulfonyl)-6,6-difluoro-2,3,5,7-tetrahydro-1h-pyrrolizine-8-carboxylate Chemical compound C1C(F)(F)CN2CCC(S(=O)(=O)C=3C=CC=CC=3)C21C(=O)OCC1=CC=CC=C1 MLMWXEYPQVNNNE-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- YIOCIFXUGBYCJR-UHFFFAOYSA-N bis(4-chlorophenyl)acetic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)C1=CC=C(Cl)C=C1 YIOCIFXUGBYCJR-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- FWXAUDSWDBGCMN-ZEQRLZLVSA-N chiraphos Chemical compound C=1C=CC=CC=1P([C@@H](C)[C@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 FWXAUDSWDBGCMN-ZEQRLZLVSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- VZMAUWSSZZABSG-ZBFHGGJFSA-N cyclopentyl (2s,4r)-2-(cyanomethylcarbamoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylate Chemical compound FC(F)(F)C1=CC=CC=C1S(=O)(=O)[C@H]1CN(C(=O)OC2CCCC2)[C@H](C(=O)NCC#N)C1 VZMAUWSSZZABSG-ZBFHGGJFSA-N 0.000 description 1
- OQIRQJNTRXOGBG-UHFFFAOYSA-N cyclopropanecarbonitrile;hydrochloride Chemical compound Cl.N#CC1CC1 OQIRQJNTRXOGBG-UHFFFAOYSA-N 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003246 elastolytic effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003386 epithelial cell of thymus gland Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- QPNJHVDIRZNKOX-LURJTMIESA-N ethyl (2s)-pyrrolidine-2-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCN1 QPNJHVDIRZNKOX-LURJTMIESA-N 0.000 description 1
- UAJREOKSJFWVNY-OCCSQVGLSA-N ethyl (2s,4r)-1-(3-oxobutanethioyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C(=S)CC(C)=O)[C@H](C(=O)OCC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F UAJREOKSJFWVNY-OCCSQVGLSA-N 0.000 description 1
- IEGRAIGQZIIPQR-OCCSQVGLSA-N ethyl (2s,4r)-1-(3-oxobutanoyl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N(C(=O)CC(C)=O)[C@H](C(=O)OCC)C[C@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F IEGRAIGQZIIPQR-OCCSQVGLSA-N 0.000 description 1
- CLSFABFUSSFLLP-DOMZBBRYSA-N ethyl (2s,4r)-4-[2-(trifluoromethyl)phenyl]sulfonyl-1-[3-(trifluoromethyl)pyridin-2-yl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OCC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=NC=CC=C1C(F)(F)F CLSFABFUSSFLLP-DOMZBBRYSA-N 0.000 description 1
- NXIVAYDLKZPUHU-ONGXEEELSA-N ethyl (2s,4s)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OCC)C[C@@H]1S(=O)(=O)C1=CC=CC=C1C(F)(F)F NXIVAYDLKZPUHU-ONGXEEELSA-N 0.000 description 1
- SFOMTBBEDGCTHQ-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CC=C(Br)C=C1 SFOMTBBEDGCTHQ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KEBHLNDPKPIPLI-UHFFFAOYSA-N hydron;2-(3h-inden-4-yloxymethyl)morpholine;chloride Chemical compound Cl.C=1C=CC=2C=CCC=2C=1OCC1CNCCO1 KEBHLNDPKPIPLI-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 108010028930 invariant chain Proteins 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- BVXXOGUSIOXYKG-YJUBXGJFSA-M lithium;(2r,4s,5r)-5-(4-fluorophenyl)-2-(2-methylpropyl)-4-methylsulfonylpyrrolidine-2-carboxylate Chemical compound [Li+].N1[C@@](CC(C)C)(C([O-])=O)C[C@H](S(C)(=O)=O)[C@H]1C1=CC=C(F)C=C1 BVXXOGUSIOXYKG-YJUBXGJFSA-M 0.000 description 1
- TULGLSWBWPBRBO-PBCQUBLHSA-M lithium;(2s,4r)-4-(2-chloro-4-pyrazol-1-ylphenyl)sulfonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylate Chemical compound [Li+].C1[C@@H](C([O-])=O)N(C(=O)OC(C)(C)C)C[C@@H]1S(=O)(=O)C1=CC=C(N2N=CC=C2)C=C1Cl TULGLSWBWPBRBO-PBCQUBLHSA-M 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- GEZDOTKDUXCCGP-MMALYQPHSA-N methanesulfonate;(1s,4s)-2-oxa-5-azoniabicyclo[2.2.1]heptan-3-one Chemical compound CS(O)(=O)=O.C1N[C@]2([H])C(=O)O[C@@]1([H])C2 GEZDOTKDUXCCGP-MMALYQPHSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
- IKKUPKMGQNWRRV-NVXWUHKLSA-N methyl (2r,4r)-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@@H]1C(=O)OC)S(=O)(=O)C=2C(=CC(OCC(F)(F)F)=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C(C)C IKKUPKMGQNWRRV-NVXWUHKLSA-N 0.000 description 1
- FGPKTWIQLMLLEG-ZMSDIMECSA-N methyl (2r,4s,5r)-5-(4-fluorophenyl)-2-(2-methylpropyl)-4-methylsulfonylpyrrolidine-2-carboxylate Chemical compound N1[C@](C(=O)OC)(CC(C)C)C[C@H](S(C)(=O)=O)[C@H]1C1=CC=C(F)C=C1 FGPKTWIQLMLLEG-ZMSDIMECSA-N 0.000 description 1
- DODCBMODXGJOKD-RGMNGODLSA-N methyl (2s)-2-amino-4-methylpentanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC(C)C DODCBMODXGJOKD-RGMNGODLSA-N 0.000 description 1
- BLWYXBNNBYXPPL-YFKPBYRVSA-N methyl (2s)-pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1 BLWYXBNNBYXPPL-YFKPBYRVSA-N 0.000 description 1
- JEDLVKBYIPCRAE-OCCSQVGLSA-N methyl (2s,4r)-1-(1,5-dimethylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C=1C=C(C)N(C)N=1 JEDLVKBYIPCRAE-OCCSQVGLSA-N 0.000 description 1
- WJJXNMCASGOECM-WBMJQRKESA-N methyl (2s,4r)-1-(2-nitrophenyl)-4-[2-(trifluoromethyl)phenyl]sulfanylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)SC=2C(=CC=CC=2)C(F)(F)F)N1C1=CC=CC=C1[N+]([O-])=O WJJXNMCASGOECM-WBMJQRKESA-N 0.000 description 1
- KKSKDULRVWVVRK-ZBFHGGJFSA-N methyl (2s,4r)-1-(5-methyl-2-pyridazin-3-ylpyrazol-3-yl)-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1=CC=CN=N1 KKSKDULRVWVVRK-ZBFHGGJFSA-N 0.000 description 1
- KXBVTIDUXFFMRA-WBVHZDCISA-N methyl (2s,4r)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC(F)=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1=CC=NC(Cl)=C1 KXBVTIDUXFFMRA-WBVHZDCISA-N 0.000 description 1
- BPEHZCOSDBZODO-MJGOQNOKSA-N methyl (2s,4r)-1-[5-methyl-2-(2-methylpyridin-4-yl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1=CC=NC(C)=C1 BPEHZCOSDBZODO-MJGOQNOKSA-N 0.000 description 1
- YVMIQVAMKNOFOS-AEFFLSMTSA-N methyl (2s,4r)-1-[5-methyl-2-(oxan-4-yl)pyrazol-3-yl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1CCOCC1 YVMIQVAMKNOFOS-AEFFLSMTSA-N 0.000 description 1
- JVOCNMJUIIZOEC-WBVHZDCISA-N methyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-(2-cyclobutyl-5-methylpyrazol-3-yl)pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)Cl)N1C1=CC(C)=NN1C1CCC1 JVOCNMJUIIZOEC-WBVHZDCISA-N 0.000 description 1
- SOJNZVSHOSCFCQ-YPMHNXCESA-N methyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-(3-oxobutanoyl)pyrrolidine-2-carboxylate Chemical compound C1N(C(=O)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1Cl SOJNZVSHOSCFCQ-YPMHNXCESA-N 0.000 description 1
- NIQZJZUKRYHCJW-CTNGQTDRSA-N methyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-1-[5-methyl-2-(2-phenylethyl)pyrazol-3-yl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC=CC=2)Cl)N1C1=CC(C)=NN1CCC1=CC=CC=C1 NIQZJZUKRYHCJW-CTNGQTDRSA-N 0.000 description 1
- WTOLGHFFYJIFLT-KGLIPLIRSA-N methyl (2s,4r)-4-(benzenesulfonyl)-1-(3-oxobutanethioyl)pyrrolidine-2-carboxylate Chemical compound C1N(C(=S)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1 WTOLGHFFYJIFLT-KGLIPLIRSA-N 0.000 description 1
- UKDOMRNNTUGERB-MSOLQXFVSA-N methyl (2s,4r)-4-(benzenesulfonyl)-1-[2-(2-chloropyridin-4-yl)-5-methylpyrazol-3-yl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C=CC=CC=2)N1C1=CC(C)=NN1C1=CC=NC(Cl)=C1 UKDOMRNNTUGERB-MSOLQXFVSA-N 0.000 description 1
- WSAIWTVMQXJFDV-MNOVXSKESA-N methyl (2s,4r)-4-(benzenesulfonyl)pyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=CC=C1 WSAIWTVMQXJFDV-MNOVXSKESA-N 0.000 description 1
- KZCFHDWZRRDNLB-SUHUHFCYSA-N methyl (2s,4r)-4-[2-chloro-4-[(2s)-1,1,1-trifluoropropan-2-yl]oxyphenyl]sulfonyl-1-[1-(trifluoromethyl)cyclopropanecarbonyl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC(O[C@@H](C)C(F)(F)F)=CC=2)Cl)N1C(=O)C1(C(F)(F)F)CC1 KZCFHDWZRRDNLB-SUHUHFCYSA-N 0.000 description 1
- VHNNSLJFXSTHIB-KOLCDFICSA-N methyl (2s,4r)-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound C1N[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(OCC(F)(F)F)C=C1C(F)(F)F VHNNSLJFXSTHIB-KOLCDFICSA-N 0.000 description 1
- DEYHSRRWIAZGDD-YPMHNXCESA-N methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-(3-oxobutanethioyl)pyrrolidine-2-carboxylate Chemical compound C1N(C(=S)CC(C)=O)[C@H](C(=O)OC)C[C@H]1S(=O)(=O)C1=CC=C(F)C=C1C(F)(F)F DEYHSRRWIAZGDD-YPMHNXCESA-N 0.000 description 1
- YDCDNELVEQVJKH-ZBFHGGJFSA-N methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-(5-methyl-2-propan-2-ylpyrazol-3-yl)pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC(F)=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C(C)C YDCDNELVEQVJKH-ZBFHGGJFSA-N 0.000 description 1
- BIZNIBWVMRLKED-MJGOQNOKSA-N methyl (2s,4r)-4-[4-fluoro-2-(trifluoromethyl)phenyl]sulfonyl-1-[5-methyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]pyrrolidine-2-carboxylate Chemical compound C([C@@H](C[C@H]1C(=O)OC)S(=O)(=O)C=2C(=CC(F)=CC=2)C(F)(F)F)N1C1=CC(C)=NN1C1=CC=C(C(F)(F)F)C=C1 BIZNIBWVMRLKED-MJGOQNOKSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- VFBILHPIHUPBPZ-UHFFFAOYSA-N n-[[2-[4-(difluoromethoxy)-3-propan-2-yloxyphenyl]-1,3-oxazol-4-yl]methyl]-2-ethoxybenzamide Chemical compound CCOC1=CC=CC=C1C(=O)NCC1=COC(C=2C=C(OC(C)C)C(OC(F)F)=CC=2)=N1 VFBILHPIHUPBPZ-UHFFFAOYSA-N 0.000 description 1
- DOWVMJFBDGWVML-UHFFFAOYSA-N n-cyclohexyl-n-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide Chemical compound C1=NC(C=2C=[N+]([O-])C=CC=2)=CN1C(=O)N(C)C1CCCCC1 DOWVMJFBDGWVML-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 1
- 230000008692 neointimal formation Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- QMLWSAXEQSBAAQ-UHFFFAOYSA-N oxetan-3-ol Chemical compound OC1COC1 QMLWSAXEQSBAAQ-UHFFFAOYSA-N 0.000 description 1
- UWOTZNQZPLAURK-UHFFFAOYSA-N oxetane-3-carboxylic acid Chemical compound OC(=O)C1COC1 UWOTZNQZPLAURK-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 210000000557 podocyte Anatomy 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 150000003238 pyrrolizines Chemical class 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- WPPDXAHGCGPUPK-UHFFFAOYSA-N red 2 Chemical compound C1=CC=CC=C1C(C1=CC=CC=C11)=C(C=2C=3C4=CC=C5C6=CC=C7C8=C(C=9C=CC=CC=9)C9=CC=CC=C9C(C=9C=CC=CC=9)=C8C8=CC=C(C6=C87)C(C=35)=CC=2)C4=C1C1=CC=CC=C1 WPPDXAHGCGPUPK-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- HSVCBDSTQCEWBM-OCCSQVGLSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,3-dichlorophenyl)sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=C(Cl)C=CC=1)Cl)NC1(C#N)CC1 HSVCBDSTQCEWBM-OCCSQVGLSA-N 0.000 description 1
- SYPYIVAJPHDALO-HIFRSBDPSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,4-dichlorophenyl)sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(Cl)=CC=1)Cl)NC1(C#N)CC1 SYPYIVAJPHDALO-HIFRSBDPSA-N 0.000 description 1
- WVVWEMHBWLYCIA-HIFRSBDPSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2,4-difluorophenyl)sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(F)=CC=1)F)NC1(C#N)CC1 WVVWEMHBWLYCIA-HIFRSBDPSA-N 0.000 description 1
- DOGFWCGIIVQKDK-KGLIPLIRSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(2-methylpropylsulfanyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@H](SCC(C)C)C[C@H]1C(=O)NC1(C#N)CC1 DOGFWCGIIVQKDK-KGLIPLIRSA-N 0.000 description 1
- RNJXFXYXTDHHSN-MOPGFXCFSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-(4-imidazol-1-ylphenyl)sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C=CC(=CC=1)N1C=NC=C1)NC1(C#N)CC1 RNJXFXYXTDHHSN-MOPGFXCFSA-N 0.000 description 1
- WWEKNJKDZRTXAM-CVEARBPZSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[2-(hydroxymethyl)phenyl]sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)CO)NC1(C#N)CC1 WWEKNJKDZRTXAM-CVEARBPZSA-N 0.000 description 1
- LPQWGIBTYYUBDN-KGLIPLIRSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[2-(trifluoromethoxy)phenyl]sulfanylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)SC=1C(=CC=CC=1)OC(F)(F)F)NC1(C#N)CC1 LPQWGIBTYYUBDN-KGLIPLIRSA-N 0.000 description 1
- UMXLIYQQBVJRDQ-ZBFHGGJFSA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(OCC(F)(F)F)=CC=1)C(F)(F)F)NC1(C#N)CC1 UMXLIYQQBVJRDQ-ZBFHGGJFSA-N 0.000 description 1
- RXOMIRGQGBUZEC-QUCCMNQESA-N tert-butyl (2s,4r)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylate Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)[C@H]2CN([C@@H](C2)C(=O)NC2(CC2)C#N)C(=O)OC(C)(C)C)C(C(F)(F)F)=C1 RXOMIRGQGBUZEC-QUCCMNQESA-N 0.000 description 1
- YFQOIXBZVAHZLT-AQYZNVCMSA-N tert-butyl (2s,4r)-2-[[cyano(cyclopropyl)methyl]carbamoyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)C(F)(F)F)NC(C#N)C1CC1 YFQOIXBZVAHZLT-AQYZNVCMSA-N 0.000 description 1
- DTVJEYIESJTRBW-HIFRSBDPSA-N tert-butyl (2s,4r)-4-(2-chloro-4-fluorophenyl)sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(F)=CC=1)Cl)NC1(C#N)CC1 DTVJEYIESJTRBW-HIFRSBDPSA-N 0.000 description 1
- IIPYWNOAOVJCEL-HIFRSBDPSA-N tert-butyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-(2-cyanopropan-2-ylcarbamoyl)pyrrolidine-1-carboxylate Chemical compound C1[C@@H](C(=O)NC(C)(C)C#N)N(C(=O)OC(C)(C)C)C[C@@H]1S(=O)(=O)C1=CC=CC=C1Cl IIPYWNOAOVJCEL-HIFRSBDPSA-N 0.000 description 1
- CBEPKDCJBPTXNQ-ZBFHGGJFSA-N tert-butyl (2s,4r)-4-(2-chlorophenyl)sulfonyl-2-[(1-cyanocyclobutyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC=CC=1)Cl)NC1(C#N)CCC1 CBEPKDCJBPTXNQ-ZBFHGGJFSA-N 0.000 description 1
- FBJLSBRVIOSAEB-AEFFLSMTSA-N tert-butyl (2s,4r)-4-[2-chloro-4-(3,3-difluoropyrrolidin-1-yl)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(=CC=1)N1CC(F)(F)CC1)Cl)NC1(C#N)CC1 FBJLSBRVIOSAEB-AEFFLSMTSA-N 0.000 description 1
- ICNKUKFBSGJYPM-GCJKJVERSA-N tert-butyl (2s,4r)-4-[4-(benzimidazol-1-yl)-2-(trifluoromethyl)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(=CC=1)N1C2=CC=CC=C2N=C1)C(F)(F)F)NC1(C#N)CC1 ICNKUKFBSGJYPM-GCJKJVERSA-N 0.000 description 1
- GXIRVIYURMQHBK-HIFRSBDPSA-N tert-butyl (2s,4r)-4-[4-bromo-2-(trifluoromethyl)phenyl]sulfonyl-2-[(1-cyanocyclopropyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)OC(C)(C)C)S(=O)(=O)C=1C(=CC(Br)=CC=1)C(F)(F)F)NC1(C#N)CC1 GXIRVIYURMQHBK-HIFRSBDPSA-N 0.000 description 1
- KLDYFLXQMIRNRL-UHFFFAOYSA-N tert-butyl 4-[2-ethoxycarbonyl-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidin-1-yl]piperidine-1-carboxylate Chemical compound CCOC(=O)C1CC(S(=O)(=O)C=2C(=CC=CC=2)C(F)(F)F)CN1C1CCN(C(=O)OC(C)(C)C)CC1 KLDYFLXQMIRNRL-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- AHDDRJBFJBDEPW-DTWKUNHWSA-N trans-2-Phenylcyclopropanecarboxylic acid Chemical compound OC(=O)[C@@H]1C[C@H]1C1=CC=CC=C1 AHDDRJBFJBDEPW-DTWKUNHWSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09158212 | 2009-04-20 | ||
PCT/EP2010/054792 WO2010121918A1 (fr) | 2009-04-20 | 2010-04-13 | Dérivés de proline comme inhibiteurs de la cathepsine |
Publications (1)
Publication Number | Publication Date |
---|---|
SG175264A1 true SG175264A1 (en) | 2011-11-28 |
Family
ID=42261969
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SG2011076114A SG175264A1 (en) | 2009-04-20 | 2010-04-13 | Proline derivatives as cathepsin inhibitors |
Country Status (34)
Country | Link |
---|---|
US (1) | US8163793B2 (fr) |
EP (1) | EP2421826B1 (fr) |
JP (1) | JP5518997B2 (fr) |
KR (1) | KR101320790B1 (fr) |
CN (1) | CN102405211B (fr) |
AR (1) | AR076319A1 (fr) |
AU (1) | AU2010241084B2 (fr) |
BR (1) | BRPI1013567B8 (fr) |
CA (1) | CA2758210C (fr) |
CL (1) | CL2011002604A1 (fr) |
CO (1) | CO6430459A2 (fr) |
CR (1) | CR20110508A (fr) |
CY (1) | CY1114764T1 (fr) |
DK (1) | DK2421826T3 (fr) |
EC (1) | ECSP11011411A (fr) |
ES (1) | ES2436550T3 (fr) |
HK (1) | HK1166322A1 (fr) |
HR (1) | HRP20140030T1 (fr) |
IL (1) | IL215065A (fr) |
MA (1) | MA33224B1 (fr) |
MX (1) | MX2011011094A (fr) |
MY (1) | MY153880A (fr) |
NZ (1) | NZ595073A (fr) |
PE (1) | PE20120911A1 (fr) |
PL (1) | PL2421826T3 (fr) |
PT (1) | PT2421826E (fr) |
RS (1) | RS53122B (fr) |
RU (1) | RU2535479C2 (fr) |
SG (1) | SG175264A1 (fr) |
SI (1) | SI2421826T1 (fr) |
TW (1) | TWI418555B (fr) |
UA (1) | UA106748C2 (fr) |
WO (1) | WO2010121918A1 (fr) |
ZA (1) | ZA201107668B (fr) |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8524710B2 (en) * | 2010-11-05 | 2013-09-03 | Hoffmann-La Roche Inc. | Pyrrolidine derivatives |
PL2776392T3 (pl) | 2011-11-11 | 2016-11-30 | Sposób wytwarzania pochodnych 1-acylo-4-fenylosulfonyloprolinoamidu i nowe związki pośrednie | |
US8729061B2 (en) | 2011-11-25 | 2014-05-20 | Hoffmann-La Roche Inc. | Pyrrolidine derivatives |
CA2859271A1 (fr) * | 2012-02-07 | 2013-08-15 | F. Hoffmann-La Roche Ag | Nouveaux derives d'azetidine |
US8802665B2 (en) * | 2012-02-17 | 2014-08-12 | Genentech, Inc. | Pyrrolidine derivatives |
JP6399660B2 (ja) | 2012-04-10 | 2018-10-03 | ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア | 癌治療用組成物および方法 |
KR20150044947A (ko) | 2012-08-21 | 2015-04-27 | 에프. 호프만-라 로슈 아게 | 신규한 피리딘 유도체 |
WO2014143659A1 (fr) | 2013-03-15 | 2014-09-18 | Araxes Pharma Llc | Inhibiteurs covalents irréversibles de la gtpase k-ras g12c |
UY35464A (es) | 2013-03-15 | 2014-10-31 | Araxes Pharma Llc | Inhibidores covalentes de kras g12c. |
TWI659021B (zh) | 2013-10-10 | 2019-05-11 | 亞瑞克西斯製藥公司 | Kras g12c之抑制劑 |
USD753137S1 (en) * | 2014-04-06 | 2016-04-05 | Hsien-Wen Chang | Display screen with transitional graphical user interface |
WO2016034602A1 (fr) * | 2014-09-05 | 2016-03-10 | F. Hoffmann-La Roche Ag | Formes solides de (1-cyano-cyclopropyl)amide d'acide (2s,4r)-4-[4-(1-méthyl-1h-pyrazol-4-yl)-2-trifluorométhyl-benzènesulfonyl]-1-(1-trifluorométhyl-cyclopropanecarbonyl)-pyrrolidine-2-carboxylique |
JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
EP3194610B1 (fr) | 2014-09-18 | 2019-11-13 | F.Hoffmann-La Roche Ag | Anticorps anti li p10 |
JP2017528498A (ja) | 2014-09-25 | 2017-09-28 | アラクセス ファーマ エルエルシー | Kras g12c変異体タンパク質のインヒビター |
US10011600B2 (en) | 2014-09-25 | 2018-07-03 | Araxes Pharma Llc | Methods and compositions for inhibition of Ras |
AU2016245864C1 (en) | 2015-04-10 | 2021-09-09 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
ES2856880T3 (es) | 2015-04-15 | 2021-09-28 | Araxes Pharma Llc | Inhibidores tricíclicos condensados de KRAS y métodos de uso de los mismos |
ES2879826T3 (es) | 2015-06-15 | 2021-11-23 | Nmd Pharma As | Compuestos para su uso en el tratamiento de trastornos neuromusculares |
US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
EP3356354A1 (fr) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibiteurs de protéines kras portant la mutation g12c |
EP3356359B1 (fr) | 2015-09-28 | 2021-10-20 | Araxes Pharma LLC | Inhibiteurs de protéines kras portant la mutation g12c |
WO2017058768A1 (fr) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibiteurs de protéines kras portant la mutation g12c |
US10858343B2 (en) | 2015-09-28 | 2020-12-08 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
US10975071B2 (en) | 2015-09-28 | 2021-04-13 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
WO2017058807A1 (fr) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibiteurs de protéines kras portant la mutation g12c |
EP3356339A1 (fr) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibiteurs de protéines mutantes kras g12c |
WO2017070256A2 (fr) | 2015-10-19 | 2017-04-27 | Araxes Pharma Llc | Méthode de criblage d'inhibiteurs de ras |
EP3377481A1 (fr) | 2015-11-16 | 2018-09-26 | Araxes Pharma LLC | Composés quinazoline substitués en position 2 comprenant un groupe hétérocyclique substitué et leur méthode d'utilisation |
US9938265B2 (en) * | 2015-11-30 | 2018-04-10 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
US9988357B2 (en) | 2015-12-09 | 2018-06-05 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
KR20180111862A (ko) * | 2016-02-26 | 2018-10-11 | 에프. 호프만-라 로슈 아게 | 신규 피롤리딘 유도체 |
WO2017172979A1 (fr) | 2016-03-30 | 2017-10-05 | Araxes Pharma Llc | Composés quinazoline substitués et procédés d'utilisation |
US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
EP3519402A1 (fr) | 2016-09-29 | 2019-08-07 | Araxes Pharma LLC | Inhibiteurs de protéines mutantes kras g12c |
US10377743B2 (en) | 2016-10-07 | 2019-08-13 | Araxes Pharma Llc | Inhibitors of RAS and methods of use thereof |
MX2019008756A (es) * | 2017-01-24 | 2019-09-11 | Astellas Pharma Inc | Compuesto de prolinamida sustituida por fenildiflurometilo. |
WO2018218071A1 (fr) | 2017-05-25 | 2018-11-29 | Araxes Pharma Llc | Composés et leurs procédés d'utilisation pour le traitement du cancer |
AU2018271990A1 (en) | 2017-05-25 | 2019-12-12 | Araxes Pharma Llc | Covalent inhibitors of KRAS |
US11730714B2 (en) | 2017-12-14 | 2023-08-22 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
US11591284B2 (en) | 2017-12-14 | 2023-02-28 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
US10385028B2 (en) | 2017-12-14 | 2019-08-20 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
US11147788B2 (en) | 2017-12-14 | 2021-10-19 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
AR114732A1 (es) | 2018-09-18 | 2020-10-07 | Hoffmann La Roche | Utilización de un inhibidor de catepsina s contra la formación de anticuerpos antifármaco |
CN114105848B (zh) * | 2021-11-24 | 2024-01-12 | 四川同晟生物医药有限公司 | 一种顺式-d-羟脯氨酸衍生物的制备方法 |
WO2023114516A2 (fr) * | 2021-12-17 | 2023-06-22 | The Board Of Trustees Of The Leland Stanford Junior University | Inhibiteurs perméants cellulaires de cystéine protéases virales |
CN115466225A (zh) * | 2022-08-16 | 2022-12-13 | 中国科学院上海药物研究所 | 一种酰胺类化合物及其制备方法、药物组合物和用途 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IE40911B1 (en) | 1974-04-11 | 1979-09-12 | Schering Ag | Imidazole derivatives and process for their manufacture |
WO1992018155A1 (fr) | 1991-04-19 | 1992-10-29 | Nova Technology Limited Partnership | Peptides de type bradykinine |
AU3359697A (en) * | 1996-07-08 | 1998-02-02 | Yamanouchi Pharmaceutical Co., Ltd. | Bone resorption inhibitors |
DK1178958T3 (da) * | 1999-03-15 | 2004-06-21 | Axys Pharm Inc | N-cyanomethylamider som proteaseinhibitorer |
WO2001047886A1 (fr) * | 1999-12-24 | 2001-07-05 | F. Hoffmann-La Roche Ag | Derives du nitrile en tant qu'inhibiteurs de la cathepsine k |
US7012075B2 (en) * | 2001-03-02 | 2006-03-14 | Merck & Co., Inc. | Cathepsin cysteine protease inhibitors |
BRPI0308208B8 (pt) * | 2002-03-05 | 2021-05-25 | Axys Pharm Inc | compostos inibidores de catepsina cisteína protease e composições farmacêuticas compreendendo os mesmos |
CA2527632A1 (fr) | 2003-06-02 | 2004-12-09 | F. Hoffmann-La Roche Ag | Derives de benzamide nitrile |
WO2006113942A2 (fr) * | 2005-04-20 | 2006-10-26 | Schering Corporation | Procede d'inhibition de l'activite de cathepsine |
BRPI0712021A2 (pt) * | 2006-05-23 | 2012-01-03 | Irm Llc | composto e composiÇÕes como inibidores da protease ativadora de canal |
-
2010
- 2010-04-13 SI SI201030488T patent/SI2421826T1/sl unknown
- 2010-04-13 KR KR1020117027505A patent/KR101320790B1/ko active IP Right Grant
- 2010-04-13 BR BRPI1013567A patent/BRPI1013567B8/pt active IP Right Grant
- 2010-04-13 PT PT107134579T patent/PT2421826E/pt unknown
- 2010-04-13 MA MA34287A patent/MA33224B1/fr unknown
- 2010-04-13 RS RS20130589A patent/RS53122B/en unknown
- 2010-04-13 NZ NZ595073A patent/NZ595073A/xx unknown
- 2010-04-13 JP JP2012506439A patent/JP5518997B2/ja active Active
- 2010-04-13 ES ES10713457.9T patent/ES2436550T3/es active Active
- 2010-04-13 MY MYPI2011004998A patent/MY153880A/en unknown
- 2010-04-13 PE PE2011001834A patent/PE20120911A1/es active IP Right Grant
- 2010-04-13 CN CN201080017460.5A patent/CN102405211B/zh active Active
- 2010-04-13 UA UAA201113185A patent/UA106748C2/uk unknown
- 2010-04-13 SG SG2011076114A patent/SG175264A1/en unknown
- 2010-04-13 CA CA2758210A patent/CA2758210C/fr active Active
- 2010-04-13 RU RU2011146872/04A patent/RU2535479C2/ru active
- 2010-04-13 DK DK10713457.9T patent/DK2421826T3/da active
- 2010-04-13 WO PCT/EP2010/054792 patent/WO2010121918A1/fr active Application Filing
- 2010-04-13 MX MX2011011094A patent/MX2011011094A/es active IP Right Grant
- 2010-04-13 AU AU2010241084A patent/AU2010241084B2/en active Active
- 2010-04-13 PL PL10713457T patent/PL2421826T3/pl unknown
- 2010-04-13 EP EP10713457.9A patent/EP2421826B1/fr active Active
- 2010-04-16 AR ARP100101275A patent/AR076319A1/es active IP Right Grant
- 2010-04-16 US US12/761,427 patent/US8163793B2/en active Active
- 2010-04-19 TW TW099112228A patent/TWI418555B/zh active
-
2011
- 2011-08-20 EC EC2011011411A patent/ECSP11011411A/es unknown
- 2011-09-08 IL IL215065A patent/IL215065A/en active IP Right Grant
- 2011-09-09 CO CO11116894A patent/CO6430459A2/es not_active Application Discontinuation
- 2011-09-28 CR CR20110508A patent/CR20110508A/es unknown
- 2011-10-19 ZA ZA2011/07668A patent/ZA201107668B/en unknown
- 2011-10-19 CL CL2011002604A patent/CL2011002604A1/es unknown
-
2012
- 2012-07-18 HK HK12107038.5A patent/HK1166322A1/xx unknown
-
2014
- 2014-01-10 HR HRP20140030AT patent/HRP20140030T1/hr unknown
- 2014-01-17 CY CY20141100041T patent/CY1114764T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2421826B1 (fr) | Dérivés de proline comme inhibiteurs de la cathepsine | |
RU2255937C2 (ru) | Новые производные гетероциклических соединений, фармацевтическая композиция, способ модуляции аутоиммунных заболеваний, способ получения этих соединений | |
AU2021203497B2 (en) | Pyran derivatives as cyp11a1 (cytochrome p450 monooxygenase 11a1) inhibitors | |
NO335946B1 (no) | Cykliske derivater, farmasøytiske preparater omfattende slike, slike forbindelser for anvendelse i terapi samt slike forbindelser for behandling av sykdommer | |
WO2005014543A1 (fr) | Compose a cycle condense utilise comme inhibiteur de la polymerase du vhc | |
JP2006507248A (ja) | ヒダントイン誘導体およびtace阻害剤としてのその使用 | |
KR20080012361A (ko) | 디아릴설폰 설폰아미드 및 그의 용도 | |
CZ2002880A3 (cs) | Sulfonamidové deriváty | |
EP2155672A1 (fr) | Dérivés de prolinamide convenant comme antagonistes de nk3 | |
WO2006071775A2 (fr) | Composes utiles pour l'antagonisme du recepteur b1 de la bradykinine | |
JP2005501017A (ja) | システインプロテアーゼの可逆的阻害剤として有効な新規なニトリル | |
WO1999006397A2 (fr) | Antagonistes d'endotheline | |
CA2859928A1 (fr) | Nouveaux derives de pyrrolidine | |
AU2009312427A1 (en) | Pyrrolidines | |
KR101337163B1 (ko) | Nk3 수용체 길항제로서 퀴나졸린 유도체 | |
WO2006013393A2 (fr) | Derives de quinoline servant d'antagonistes de recepteurs de neurokinine |